Oral development and histology, 3rd edition

Oral Development
and Histology
James I<. Avery
Third edition

~Thieme ,


Oral Development
and Histology
Third edition

James K. Avery. D.D.S., Ph.D.
~ ~o.ntisuy..-l.
SChool 01Dl..Ir'oMnlly of ~
Ann Arbo<. Midl ~ USA

Editor

P.....line f. Steele. 8.S., R.O-H., 8.S. (Educ.). M.A.
ProfSChoolof Dentktry
Un~ity ofMi<:hi9,m

'",," Arbor. Michigan. USA

Awx"'te Editor
Nancy Avery, B.F.A.

Ann A,b()r. Michigan, USA

850 .....I'al;oo ' , p
III "t~M
"n
01593
Thieme
St urt qart - New York


Libmry of CmlUCss (o tologing-in-Publim r;on Dara
0 '.11developme nt and histology I e d ito',J~mes K. Avery: asso d ate edito t, Pauline E Steele- 3rd ed,
p.: cm.
Includes bibliograp hical refere nces ~ n d index.
ISBN 3131001933
ISBN 1-S889O·028-2 (TNY)
1. MOUl h··An~tomy. 2. Teeth-Anatomy, 3. Mout h-H isto logy.
4 , Teeth --Histology. 5. Embryology, Humdn. I. Avery. James K.
II. Steele, Pauline F.
[DNLM: L Stoma tognath ic System--a natomy & hislology. 2.
Stom .togn~thic System--g rowth & development. WU 101 063
200 11
RK280 ,0683 200 1
6 11'.31 --d(2 1
200 1027523

rcrvr-

Im po rt ant Note: Medicine is In eve r·chJ nging science undergoing continua l de velo plMnl. Research and clinic,' 1 expe ri_

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12 3 4 5


Preface

mlI~ [he Sltdent of d~[i$by to
lel, n the hmdamcm.ls un6cJlying cI,nic. llrealmenl of [he
pat ient Oral Slructu",s . re d.""riOed in microscopic de tail in

Ihis book. A' in the p,o>«tioos. The first secti oo desaibes ~lopmenUI details of
Ihe heood md nKk md how \htsle WUCfurn ",late 10 the body
;os a whole. Akodnaibtod is tM ",lariombip of celli to ms.how ~ ~ up otJolIIS., .nd how org.>rtS ~ to tbe
IOUI bring. The develOl'UlS body is to!low<;d posma..11y
through posl. do le>.<""",. The second SKIion dnaibe< [he
de""loping crown, and roots of tile t_ h . nd 1M tilSue, sur_
roUnd ing . nd , uppo rting them , Tooth eruptio n and , hedding
is .1<0 Included In rhi. secncn The third se<;tion is i descri ption of rile form .IS _11 .IS • comparison of the pnmary .and pe1"ITW>f1lI
drtItklons. The I'ourm >«tion do'Kribes the oupp<:lftllll tissut<
of [he rem. inc1uding rile lingiw .nd dte pO!'riodonlium.
which ~ of the cementum.•1WQI.o. bone.• nd periodon•• I Iig.lmen•. Tbese " ""lures. Ind udil!ll tlleir innerv.tKrn. • re
fully des cribed. The fLfth section descr ibes th e gland, of the
or.1 e••ily . nd 'l\eir produc t<. The s.ixt h .nd 1i ",,1 """tion

The lim of tIlis IUt is 10


es . 00 the temporomand,bul.r joi nl S, Also consideted in Ihis
section .... tooth movement. tooth implant. lion. a<\d he.ling
of or. l tissue s. In comPJ.ri",n wi th tile pa.1 edilion. we beliew
this OfitheSf'sullje=.
This _ l'<Iition is updored.nd""l>'nded. l:>rin.li", l'orth _
information gained since pmduction of the IN l'JIM, included ~ "CIin>cil ApJJIiations" to better relate
basic . nd c1illicalloformatioo. The "''' I contains.
nwnbe, of illustr atiOn! that enh. nce understanding of the wri lten

descript ions. In this edition color h.s been added to furt lle,
cI.rify tile hislO!oPc phoromkrogr. ph' ,nd Ihe di. g•• ms. This
sho uld .o:sisl in .,uning infolll'WOOn .aboul lhe struoute 01
complex tissues. A JlOSQlY is...,;n iDdudM to assist in defining l.MnS l!I.>t ""y be unWniliar '" tbe stu. ",hon wish to fllllf= their hoP<' ttuI the ma ~ 1:s pmo1lt_
ed .~ ~ar . nd undermnd.bl•. PIe.... wnd . ny questions
Ih• • • n.. to me o r to the . uthors di""tly.

".po

F.1l2001


Vc'

_

Acknowl edgements

The first ed ition of l his text was developed with th e a«lst.nce
of a group of student s of the oral histology cu ss at lbe
University of Michig.n School of Dent istry. Dr. Donald
Stracha n. one of l he instructors of lhe cou rse. had encouraged
developm ent of a series of slide-tape sequences to stim ulate
interest in th e sUbjeet. From this effo rt class m" Duals were

developed. which then evolved into a textroo k. Most of lhe
slu de llts involved are now teaching at u niversitie s or are in dental pr.clices Some of them have w rine n eh_Plers of lhis book.
Again, the med ical illust ratio ns in th is OOok were p rodu ced by
stude nts of dentistry. The first waS Jeff Clark w ho prod uced

much of l he a11 througho ltt the book. The secood
Alayne
Evans, then a dental studenl , w ho listened to l he needs of each
of the authors and provided excellenl illuslrdlions. Both dre
prJct idng dentistry toddY. Much of the phOlOgrJ phy was dlso

w.,

donc by students such as Steve Olsen , Cary Bilyk, dod Tho mas
Simmo ns. dll of w hom creared the photogTdph)l for yca rbook s
at the univers ily and found it d chaiicngo to produ ce the
delil M d iH lI strations requ ireI ~ m also grate ful lo Drs, Dan iel (hicgo. Donaid Strachan, and
Chdries ( ax, wh o assisted in teJching th i, m urse and m n·
tr ibuted in mdny WdyS to the evoimion of this text. G"i,lonc-e
was also provided by Dr, Thom as Greenc of the Department of
Educ~lionJI ReSOUl"ceS w ho evaiual ed ma nusc ripts an d in
maO)f ways os, i,ted in lhe productio n of cia.., IOJ nusc ripts and
uitimatel y this text. /lit hough maO)f of the,e peop le were nol
on the scene for this edit ion. they heiped immeasm ably on
earlier ed itions from w hich lh i., ed il ion was developed .

10m,'> K Av",y


_ ___ _ ______ _ ____ ___

~

v"

Contributors

~me<

Robert B. O'Nc.... ().M.D~ M5., M..ftl .

K.!lOftY, 1l.D5. 1'lI.D.
Prol'C'SSOI EmtrinJs, DenllSlI'y lind ...... l~
Sdtool of DmIimy lind ......,iuII SChool
l.IniYenity of Midl ig.on
Jllln Arbor. Midli!li'n. LISI\

~ty o f ~

Sol Brrnic k, Ph .D.

Nicbol.u P. Piesco. Ph.D.
.....5OC;" te
Depart ments of 0 ..1 Med id ne " nd PJthology .nd RellO,af; vt'

Professor Emeritus of Anatomy
Department of An~ lOmy
Uni ~i ly

1.00

of Southern California

Anv'"- Cal ifomi.l.USA

o..niel 1- ChltIu. Jr. M5.. PIl.D.
" " " " - I'ruttnor of Dmlisny
o.p.uTrntnl' of C>r
DirK'lor
Sowtl~

~ d ",, ~

Pmodonlics

W.o
Prof.",,,r

0.0(. 1SCience'
SdIooI of Den UI Med lclne
Uni...... '!y of Pimburgh
Pitubutgll. PenIlsyIvlIni.l

s.s..

.nd EndoSchool of Dentistry
Univl",i ty of Mi chjg.>n

F... nciKo IliftB-Hicblg6,
D.M.D~ M.S... F.l.C.D.
OirKlor

Dfop;I~ of hriodonrk5
Iloylor Colkgr of Dem lmy
The Tex.os " l!l M Un ~ ..;ty SyMem, H."lrh Scienre Cenf<'r

Arm Aroor. Mich igcin. USA

D.Has. rex. ' . USA

M.rion J. Edge. 0.101,0.
O>air~'lOn lind ADtp.artmmt of Di.lgn
j,o mn W. SimIDC'l ink. Ph.D.
Associate ProfeSliOr of R...roratiw Dent'Slry
Di~ of
SChool or Dentist ry
~ 'Wrstnn Rnerw l.-.i¥nVty

I'rosfhodonlia lind ReslorOliw- O"'"is1ry
School of Dmlistly
l./niYn'Louisville, Kmtudy, USA
Cdr]d A. EVd.... D,D.S. D.M.Sc.
Profes"" of o.nt ist ry
Chair of Ort l1O<1 ont k '
Uni""rs it y o f lliinoi'
Olic.lgO. Illinois, USA

o.vid c.johnsrn. 0. 05., M.S.
0.." ;md """"'sor of l'Pdiau;c: Dmtimy

Uniw1'College at Dentiwy
low.l City. I_ol., USA
R()bert M .I( I ~ ln, Ph.D.
Profess or a nd Diren or of Medic,,1Educat ion
Dcpartm.nt <>f An.ltomy and Cell Biology

SdIool 0( M«I i<:ine
Un~rsiIY of k.1~ Medi<:dl Cnlter
Kms.a. City. Ka...... USA
rIlII'i.... ""~u

_~ ~ ...

_"rdl

0tYNnd. 0Ili0, USA
Gwffrey tl S ~. e.se, lions. &05., M.s.. Ph.D~ FJ .c.o.
Pto~or EID<'fit""
Facol ry of Med icine and Denti' t ry
Un i ~ r s lty of Alber ta
Edmo mon , Ca nad a
Domld S. StnodwI. DDs.. I'ILD.
Professor Emeritus of Dmtimy
SChool of Dmtimy
Mwci.1~ I'totnMr at ....... romy a nd IAlI Bioloo'
Medic... SChool
Uniwn:ity of Miclliloiln
Ann Arbor. Mich illa n. USA
[)(,nn is F. Tu rne r. D.D.S.. M.R A.

Clinical A' soci at e Prof~s",r of Denti Stry
oepalt~nt of Cardiology
Rie«AuiSWll oedn for Pdfim t Strvia's
ScboDl of Denti>tJy
~ofMldtisan

Aon Arbor. Midlipn. USA


Vlll

_

Contents

Section r
Deve lopment and Maturation ofthe Craniofacial Region
1 GeT1e r,11HUnl;ln Develop nlent._..."",,..,,"....._...,," ...._.....". 2
j Qme$/( Avery Qnd NrlgQf M. f INe"

2 Development of th e Pharynge.1 Au;hes and r ace

"

21

j omes K. Avery

3 Develop ment of C;lrlil;lge ;lnd Bones o f Ute

Craniofacial Skele to n.._.........

44

ja mes K. Avery

4 I\Jstn.t,,1Faoal Growth. Birth lhrough l\J, tadolesceoc e.,... 6 1
CarlQ A. fwm.>

Section II
Development of the Teeth and Supporting Structures
5 De,elopment OfT""t h: Crown Form.d on...,.....
NichQ!Q, P. Piesro Qndj a mes K. Avery
6 Development of t he Teeth: Root . nd Sup porting
" " " .,
St ruct ures
",__ ", "
Nag
72

7 Tool h Eruption a nd Shed ding...
Nagai M. fl Nesr Qnd Ja mes K. Avery

8 Agen l\ Affecting Toot h J nd Bo ne De,elop men t.
"

108

'"

j Qmes K. Avery

Section III
Structure and Function of the Teeth
9 Histo logy of En. mel" "" "" ", ", ", ".....
" 153
Nld wlas P. l'i esm alld jam es Simmelink
10 Histoiogy of Dentin.....",.....",.....",.....",....",.....",...."" ......"....." 172
NichQ!Q' P. Piesm

11 Histology of t he Plllp""...."" ....",...."" .....",....""....

190

D.). Chiego.jr.

12 Co mparison of Primary .nd Perm. nent Teeth
David C.jQhnsen

."

,

213

Section IV
Structure and Function of Supporting Tissues of the Teeth
15 Histo logy of Ihe Ging l, a a nd Epit h ellal llttachme n t. ,.,. 263

13 tlisrology of th e Period ontium ' Alveol. r Bone.

Ceme ntllm, a nd Per iod ontal lig.me nt .•,.,. ...,.,......,...... ,. 226
j ames K. Avery

14 Histology of the Orai Mucosa and Tonsils.,".,.,.,.,.,.,.""".,".,.,. 243
Donald S. Strachan and james K. Avery

j ames K. Avery

16 I rrn~rvation of Oral Tiss lles,....."" ...."" ... ",....."" ...."" ....",....., 274
Danie! J. Chiego, jl', Dellilis f. Tum er.
and Donold S. Stracil all

Section V
St ructure of the Glands of the Oral Cavity and Their Products
17 Develop ment, St ruct u re. a rrd flm n ion of t he
Saiivary Glands.." " "
" ", ", ", ",,
Robert M. Klei n

,,

", 292

13 Histology of Saliva, Pellicle. Plaque , and Calcul"s ..
lome; K. Mery


Section V1

Related Functio na l Tissues of t he Oral a nd Pa raoral Areas
19 Histolo gy of rbe N ~ s a l Muco<.l and Pa r~n~ 'kl l Sinuses ... 341
G€off'~ H. SpeIW r
2OSr.ructu ~ ~ nd Function of , he TemlJORlrmndibular

Jcn9'

153

n

)tnnn k. ,,~""" Sol Brrnict

Glossa ry

- -- - - - - _

I n d ex.".".......

I

21 HiSfOlagic Ch~ngCa.loAEvons
22 Histology of EndosW'OUs lmp l. nn..

..

_- ",

.." "" ,.". ..." "..". .. _ ".... .. " , 427

llobm It 01tftJl"lId M'Hound H~.li...

' rulldsm 1IiwnI-HidoI/g6

"

364

.._ .._

n>

E«P

m


- - -- - - -- - -- - -- - - - - - - -,

SECTION I
Development and Maturation of the Craniofacial
Region


2

I Develo~nr cnd Maturation ofthe Cron;pf(l(lal

esss.

_

1 General Human Development
ja lnO'S k. Awry . OO Nagat M . E1Ne.r

r-'"",PI~ Oulli ~

---------~

Inl roductIon-.. Z
ObjKtIw$..• Z
Origin of !he Ii """,.. Embf}Funda","",Yk of ~ •.4
~ofPr.naUI~I
0<-1.... of tM Prohf....-~ion ~
Emb
5
5

fml ~ .. 7
DewIop","",t of th e Ne"""" Sysl..... ... 7
Dtwlapmertt of t tlt ea. l roi"",. ti nal System, .. 9
Oevtlopme..t of tI1e Muscular Syst~m ... 9
Skeletal Muse;. 10
Smooth Mu.d~ 10
Cardiac M u , d ~ , . , 10
De""lop me nt of t he Heart and Blood- Vascul., Syst~m... I J

Heart ,., 12
S "~letal Developmen t... 12
cartilage... 11
Bon~ ...

J3

Morphol ogiCChang es d uring Prenatal Dtwlop ment... 11
Birt h... 15
Abno"TIIII Oewlopment.... 16
li ertditary Ou~ of ConQeoital Mal!o<matior><... 16
ChromosomaIAbnormar~; .... .. 16
G....->ttiC Abnormalitits... 17
Envi""""""'al Causn of Congenital MaIfonnation• .•. 18

Inf«tJousAatnts... 18

Radiltion_.18

Drugs.•. 18

liormOr'ItS.•, 19
NutriborIII D;sorderl.._ J9

T....-aogenk: Hatm: SmolSumma
StIf·Ev.olualton ~. _ ZO

Introduction

Tht 1lU'PO'" of !his chap!.... is to dtscribe lIIMlY of tilt
imponant ckw"",mental ewnes th at t.>kt place
bttwttn eonctptio n and b1nh In tilt hulNIL f.orly
.........15 Itad ing up 10 and foil_I ns COlKtplioo ""' discusstd. such .... end""""rial d..."P' in p..."..",tion lOr
impla nta lion of lhe fertitized ovum. Changes io th e
mdocrine kvd of esrrogm and proseSl<'fOne are noted
and facilitate cha~ in the ut~ri ne wall and the fenilized ovum , Growth of the fertilized ,,"um into "n
embryobim~ mbr"ne system i, next described. T1le embryo is the n
seen to uOO~rgo differentiation of vario u, orgt hat w ill give r i5" to t he brain , th e sp inJ I cord , .. nd t he
gastrointestinal lUhe and it•• sscclared 0llla n•. Som ite ' .
~ seri e, of soft-tissue block. l<>Cl ted on eit her . ide o f t he
neural tube. ~ppear ~12 , 5 """, "s. The", so mite, enl arg.
10 prov ide muscle ~lId skelel~1 ~uppon of t he body.
Blood i,laOO, ap pe~r in t he yolk laC and plllCenta.. Blood
vtSS<'1, and a>U. ot t he ~ascu l~r sy<;tem d,"",lop .000 then
prep.1~ (or the initl.otion of
first he~nbcat. Blood cir·
culare-s first from l he yol k sac (vite lline ( ;rcu tation) to
pmv;de nutrition for l he nm few ~ks of embf}life. lbe vascular ;ysI..... then conductll oxwe tM
blood from me pLacenl.i. As me embto
grow. ~ number of tissue type s ~ppeir, .....I>linz !he
embryo trJ .........p many spemonths ItIe feru> Ius deve\ol>td "","",lal rea tures and
gmwn in siz<-, mlar$>", sufflC!mlly 10 be prepved for
!he dIange'I ~ted wit h blnh. f1JwI1y, a numb....- of
~iwy .ond mYinInmmlal lacton !mown 10 ( ause

me

~ 6tfuet:s

.ore dMcrfbed.

Objectives
After read ins this chapter. you should be .>I:Jle 10 di'lCUSS
!he importaot drwlopment~1 ew-nrs suell .... femliutiOO
and further gn:rwlh of ~ fefli1~ ovum. You .hould
.01.., be able to discuss tM deve lopment of the ~ .
inc! organ systems of t he ..... bryo ~nd rhe fet us. some of
th e ~it~l ""'nges ~t bi.th. and n...I]y. ""'"'". or t he
im portant l>ertabnorma l development.


________ _ _ _ _ _ _ _ _

-', ,,
""
"
~
".
"'
Human DMlopment~

Origin of the Human Embryo

I

Hum..n preD.. t.. , development bogins wllh processes
i"""lwd in Itw, ov.trl.ul cycle .on"" me 0VUfIl ductS ..00 upilw r>es prt>lif"'. le in m. ~nclnl)'i n,
mclc>mffiium. Tht .. r....... is thus ~na: fOr lilt'
.."iv.l of ~ ftortilized ovum. 1M umiAe d",ngeS rrom
tile ha rmon .... m ogen . nd progesterone nl"1uale cscnc.lly; bod! funcb".. In ulerlM' .... ~ Il de""l.,..,me n!
[fi&.1.1 ~ f'>0jll'St<10Re " Iso ~s in II..- tn\IlIY.-rWn roI~ inlO thr lilt' ·ccapII$ l....,..m.· The
_ .
~1'U.l.I ~ is 28 with lbe indlvld..... L If the' cyde is ddined fl"Om me fira
day of momSlTuolI flow. ovul.u ion will OCt .., .OOU{ 14
days later, Ry th is l;me, " follicle rupt ure$ on the surfa.e
of {be OVdry rel...,i nll , m..ture ovum. Note both <)\Id rl.ln
. nd uterine ch;lnge~rtiliulion fi!Wlly occurs in lbe diml ..........third of
ee lKrone ""'" (ft&. 1.2 ~ III1W)' occur .. I$( "bel~ IeIdITlI to .. n "ClOPic prqn..ncy. It besins witll me deposilion of some 200 m ,lllon spmn. t.ozoo in 1M v.agin.l d.. , ·
ing coit us. Tho ,~rm.tazo:a """'. 1.5 10 l rom per
minu te tOWilrd ~ n d into the uteru• • nd u(er l"" tub es to
the poinl of fetti liu tioo. Iiowcwt only 300 to 500 s~r·
nNtUOil ",nuin vi.bIe to sunound thr O'VU"'- Finilly.
onty .".. ",","""WOlIn (V. -;a)lyl P"'f"'U.~ thr ovum.
~ owm Is surmuncIN by lhe zorw. ~lllCick whOctl
.hft rettiliUlion becomn . fn! iliution mombr.... th.ol
Pl'~t. other . pnnN t"''''' from .... tering Ihe ovu m.
FUl ion of the mili. ilnd femilie pron udel then occurs.

e",h prontlClw. car ryll1l 23 chromo><>nles. Th;. proce1.
COflIPIetC'S l he fn!iJit,uion proo!"is. Tho fmiliuis Ift1DCd • "zygocr: whidl t hen undcrp;Ieos de....
(WI di'mion).md besins MCI'l'eInml inIo !be uterine
fUbe, w~ It p.t>S1e$ t-.rd the ul<'rine UYity. fl uid on
the oviduct: .s>lon the Z)'gOIe on j f!; JJ>OWml'fII 10 lhe
uterine (a~ ity, It t.l.k~ 4 da ys for the ch.l.nglng z\,&ote to
...",h the ut er ine (a~;ty w here u wlU ;mplan t into the
w.1I of Ihe utMUS (fig. 1.2 ~ ~ lygofC mNnw hlle Ius

"
I!
II

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",I
o

,..

~~ a ~ 0 • •,

~

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" "

-

--

...-,00........


4

I ~t ond Maturatloo

o{rhe Cronio{aciol ~iOll
"'-

m.ngnl in'" • multi-ulltd rn=; this is tnmnl the
II>OfU1.J .... (fiJ U~ .... 1M mlula, ""'.. d ividoos. "

~·
W

enlarges _

~
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•. •
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~

rog .1 4 ~

pins " nuid-fil~ m,-- c.ovily ~rmtd the
blom>cdo. Tht' bllostocde wpllr. ..... the cell< dUO lWO
JWIU: on ""1ft" «Il~. ee h O"'~ .oo ~ inner
all mHS. the embr)' t ' .... This iI all«! the ~
~ (fi&-1.4) mel occurs j ( 45 d.>y5 .tier ~Plion
" nd shonly ~ irnpLinution.
On the sixth lUy. impllnYtion tol= pWC1!. Tlw 110pbolIl.rto the sli cky ,0donlC,\]1.1 sul'f.1C1!. \I$Uo>lIy on the ~
or wall oJ rhe body Dllhe u~ru. ( Fig. 12). The uterine
wall. in l he "",,,nl ime. h.l. i"".... S<'d it' va",ularity in
.~ pec eal io n of f'f'Celvlnllhe cen mJ.''- The . urf. c. ceus
of the t,ophoN,," prodU«' hydro lyti<: , "'ymes th.ll
digest the eod omen i. 1ce lll, olUow ing " d " p" r p<'"etr. _
tion of the ""II rna" (Fig. 1.4 ). This event is termed
- im pla nta tion."

Fundamentals of Development

,-

_

-

In the I"' st <:\outI ~. rs me molb",,,, ~mml hn bHn the subjM: of inm- study.
yet lOday"'" ~ orinno! ab~ 10 undersl:.ond I1WIY of the

/lfO='S<'S Yi~ to fUlllWntrtW ~ _ F« esempit." sm" moy " - dL1feftn1funcrioos a' tlirrn- periods '" ~ f . Ako import.Jnl. but no( unclontood,
is ee ... of mUUlll Iorms 0( lk.elop",enu!ly Imporf. nf ~ (po _ o< op nul which «1"""'-': ~ eeus
to rumor cr ib. Rutoft' lh.1n .mmlXing d istUSSion oflhis
",p.o_ su b;toct. on ly """mples or rnoIa"ulMcon lrol of
ch.pleJ$ in Ih is h'X t Many of l he moleo:ule<. Ih.>f gu ide
e mbryo nk dtvriopmenl C' n br ~up<'d inro • sm.lll
numbrr of cot~ries. Some molemles ....m. in In lhe
cd. fha l pr<)duce t hem and a<:tas Ira n ocrip l ion f' <101'!1,
Transcription factors are fho,e p ro ~i n, thaI POlse15
domains a nd bind 10 DNA (de nxyr ibon ucldc .cin) in
en h. nce r regin n< of genes. The....a re mony kind. of 1I. nscription factQf1;. Some act.s ime=lIular effect ors s!lmu lafing .ldj.lce m cell. or Ih_ cell, d ist.nt from t he one
from w hich they origi,,"~, Howewr. e.lCh contain sl, .
""mng JJlo lerules lhal .ffect growth_ Sign.lliing moleroles are mnIi.tors of IllOS( ime rxtions OT indUClions
between f'MI groups of embryonic cells. Tra nslonm"ll
growdl fa. ... Jttodgdq pnxeins ..... famil ies of molecules dl.J1
~ imporunl induettve phenomena. I'Inw , . - h
bctor is;l/l rownpIe 0( ..... wbich stimulatrs me JI'OWfh
of >nlSOl)'.nd 'I)'R1ll"the(lc ~ and ~ - . . srudiN
for mony ~~ Other ~ function as re«prOrl
1oc.I~ 00 ceO surtaees and can function from .. ther an
inm«llular or extr~llul.. . location. Eumples of some
or [/,.,,;e molecules ..,II br de srnlJed as their dtvriopment is d iscu ssed

I


Periods of Preoeta l DewIopmeot
Impl.om.. rion ind mLolJ"mtnt: alllv ~ whid!

con ..ins ~ embryonic l issues. _un with in II", iiI"$! 2
....eb o r Mvelopmenl .00 ;. deKribed .. the ·proli~.
il~ peliod.- During Ih;' l i_ , fffliliZplace_Aflor the s"cond w""k t he embryonk m. s.s begm.
10 t. ke t he ' I,..,. of on embryo, so tlte .,.riO(! of 3 to 8
is i pprOjlriolely tem...During t his pe riod tn. embryonic ,.,nn Loye'" co mpowd
of It'CI odE'< ,,~ mesodornn. ilnd en d<><\l:i m di~ntim
.00 form tim>H. wbi ch Ibm form orpn ~ w,lhin
the rmbryo. N. .. Wft'ks the lINn form • .00 brJins lO
bfm. the _ill tubt form$. the pslroin~ lroKt
den lcps. .oo the W lOons, N. 8 -..b the emllfyo
beSins '" loot human, iOOicitillJ the beginnillJ of the
fe..1 ~ th,u .."Iends u nfll binh (Fig. L5~ AI.., 00
incre. "" in body ~ght oDd m e refl«1S llIe increi~ o r
li"lI<'5 ond org;on systems d uring Ihe fetal pe riod_

""""k'

r"l-l _"~01"'_"I_"'_II '

Deta ils of t he Prolife r at ion Pe1'lod
In the SNUnd -..k blaSfO<y>l a-llsofrlle inner oellmilSS
d ifJerenli.ll e into two oed moo,"" e.Kh co mpri .ed aI di' ·
fermr cdl types (fiI. 1.6~ 'J1>eK.m col"",rw 1t'CfOdftrml a Ils ilnd Cllboidilf mdodmlW «iJs thilllie slde by
_
fonni"l I"" mlbryonic disc (Fi:J. 1.6 ~ A cil'Vity,
~ the ilI1lniolic cwity.dnelgps ~ the «tod=n.1 cel ls aI I"" flJlbryonk disc . 00 the mls of llle
OUI... Willi of llle tropboblilSl: (Fig. 1.6). Thefl il SIt'COIld
;nle rnal coviry. I"" yol k ..,c. • ppe ors (Fig. 1.7). n...~ cells

give rise to yolk, ur nulri tion or t he . mbryo, unl ll blood
ve"els '·orm and ea,lY food rrom the mo the r's clrt ulation to tile em bryo. IloCh cavil"'! lie on eit her . id e of th e
HI1 bryoo ic d iK (Fig_1. 7 ~ n,., om niol ic cavity, liMrr...mbr. ..... mLorpos even more ropidly Ihon Ille C1IIbryo
ilOO i"""sn II iu mnnbr.ltle.1be Mveloping embryo is

e

~ 1.5 Tho: """1* '9 _ _ P"'_llloGurjh _
pet\O:Il:
lht proIIfer_t~pmod.-..heItnt tAl;""'. mbo ,,"'" peOod. _h ...1to"", e;ghth _
(8); "",lei" ,,",lOd. lrom the oighth-«

tobi.- lh (C).

\

fC"I_1.7 ~"'"
.11 "

,,"",,

6

I Development and Maturotian af the CraniofackJl R<'gian'

~-"'"
~pnmij;""

",.o k

P rochordo l p late
NOloohordo l pn>ce..
P,i m~i""

koot

_

prov ide d with nut rition by cells of the oviduct an d ut erine giands uatil th ~ he"rt beg ins 10 funct ion at 4 week s
and nutritioo i< ,u ppHed via the umbilical blood <\ll'p ly.
During t be em bedded in the en dometri um of the ut er ine wdll.
Fibrin plugs the e ndom~rriai i mpl~ntatio n 'i te. The placenl. develo ps from the vasculdri, ed ti,sue tb" rounds the en larging blastocyst. The placent" is Ihe lOne
of exchdnge of matem~1 oxygen .nd carbo n dioxide from
lhe em bryo. From the sm fdce of th e bl.. ,tocy, t, cells
grow ~ $ finger_li ke eXlensions from the ,u r fo < ~ of tbe
tropho bl" , t to inv~de the spongy vascu lar placenta, As
Ihebecome funclional d uring the third week (Fig 1.7).

Embryonic Pe riod
Th~ ~mbry<)nic

Fig. 1.9 Formationof tl.. mo""'", m.

Prochor dal plat.
Neura l plate

I",riod ran ges from 3 to 3 week> ond i'
the d iffere miat io n period for the three w sic tissue typ ~s
and thei r specidlil atio n into org.J ns and organ syslems.
The embryo nic d isc i< mod ified d llrirlg the 15th doy as ~
groove, called tbe "primitive streak ~ knOI of cells ap pears, w hi"Henson', node." From thi< no de. cells prod" d rlg the
notochord grow omeri otly to provide the prim it ive dxis
of the em bryo (Figs, 1.8- 1.10 ), M~sodermal cell, from
the prim itive str~a k and noto chordal process grow lofer"
dlly between the "'loderma l and endod erma l I"yers
for mirlg the embryonic sbield or Ihim ger m layer, called
the "me ' oder mal layer" (f ig, 1.9), Duri ng the ll,im week,
mesod erm~1 c~lI< grow anteriorly, post er iorly,and 1001er·
ally from the midline, co ntriburing to the formi rlg
embryo and un iting laterally wil h l he e" tl'aembryonk
me soderm of the amniot ic membrane " nd yolk sac wall.
Mesode rm, bowever, fail< to intervene betwe en Ihe ecto derm and endode rm at the rostral Olnd caudal, giving rise
to tbe prechordaland cloacal membr,ne, of tbe or" l c~v"
ity " nd on uS. Tbe neural lu be ar ises d ist,,1 to the notochord by the infoiding of neural fold , : from here these
crests give rise to ne lLral cresl <"lis tb ,'t behave like
me soder m, ~ n d are hence called ~ ( to m~ , e n c b y m e .
Anterior crOlnial derivalives of this tiss"e a", the conneC"
live tissues and bone' of tbe f"ce.
The ect odermal cells contribut e to tbe nervou< sysle m, lhe covering of Ihe em bryo and its appe ndage.'

(ndils, hair, ' eb"ceous ~ n d sweat gland, ). the ep ithelium
lining the oral and nilsdl cavitie s and sinu ses. a parI of
tbe intraoral glands, dnd the ~ n a m ~ 1 of tbe leet b. The


1 Cenerol Human Devel~t

embfyonic enIl'Olmesd....1 tr.ld. th e uonwch. ~ .lSSOCioI1ed orpn.
slldl oK lUll&'. ~11O'NS. liver. JoIl1bbddn• • nd urilW}'
bbddn (f'iJ. 1.
Durins !he nnt ~ weets ee ~ ~ .rn..s
~.u .IS Iloril>:lnt.olly po!Ilrionfd tullulN II'I>$Sl'< lomr
ins lhe ""'lIdibk of l he bee -:l ti:uuet of !he ned. The
aeodt;"",al Lo~ giYes ripe11odonl.l lig.l=nl . re of neu l.1 (reThe f.loCl!! I. kes form.md develops duriTIJ tbe fifth to >C'V",th ,...,.,ks.!Is these lisSlOO'$ begin to fonn. the embry on ic period bee"",.. the ret.1 period . t lh e eight h ....eek.
This is m. rl;oo by the first ~p pearance of ossifLcation
cen t ~ rs thai fonn bon~s.

7

~

~. s.-y
e.-n......_
~"'---. ­

.....
-.,.....

__r-,' - -

m

-., -... '" . . .
• .gird>
.• Eplll'
. ...
__

II

.. " ,

~.

• G'

..... _

_aet ~

fill. 1.11 Deriv.r;"", 01germ I¥

._gIMdo

".

Fe u l Period
The embfyo nk period i.o the u dl'I«t for the felOl pe riod. All =;Or and mosr of the minor orpn' bq:in lkwIo proenl in Ihe embfyo nic period..nd then It'''W . nd

..,..a.li%l.' d uring !he feul period. This Is the period of
~h. II i' ..id tbil ' i f _ COnl inued to ""'" for !he
I'l'U 01 our lives .t this ,a'" Ndl 01 uS would ~ 1.0.....
11wI lIIe ~ in whidt _ e,,,U. N. !he end 01 !he kW
penod. " '" lle.cl is ~leIy ~ COIfIlW"'IIO
the Itss _ U-de... k>t;>«I posra.lllial rqion ("--I S8~ If
tile embryonic pmod is tile suae of oopn differmfW_
tion, men the kW period is lhe ~ 01 org.>n growth
.nd ph)1iologic ""'IU"lion. T1le ...... indcr of this c:bapIei' Is • descripl io n of ,he ¥.lIOoUS orpn . ystnns INI
~Iop .nd ""'lure during lhe feul period. TItis period
~res the fcl US for its enrr. nee imo Iif.. as an ioo..pendl'nl "" ing.

fig.

_.-

t.1 2O".lupolle'~ofthe

................,.

-----z!',;§"-"""

~;

~'-... ~

Developme nt of t he Nervous Syste m

Nou",lgr-.

Th~

proce" by w hich the emhryonk head and r.ce a",
p.otlemcd i' a ",mhnuu m. ""ginning wi m ,peo:fic.otion
0I1 he .nlerior ~ ral pla le. T1le inilially n.t neu r. 1plale
~Iops <'lev.te.l1y lou1<'d cel ls become 1oc.1~ OOrs.llly .. m.. pl. te
rur1, 10 fonn • lU""- This rube i. lhe tornun...... 01 !he
brain.nd ",i...1 conl (Flp. 1.I2 . nd l n~ ~I"'oclll""
medially in !he ""w;oI pion. w~1 je IocJt~ _~ly in
l he dn.... ..."",lWllO I"" p.otl<'fninl: 01 1M ~ rube. The
medially Ioc. t<'fnlm in pooition undmying the lWUt~ p1a~ ( fig. 1.I~
The nnu.ol pion. bends aJona: in (ftllr~ allis to li)rm.
cr-.•nd Ihc r. i""" marsi", lbI1n lhe .........Iru""- Tbl'
nt\Ir~l folds llrMlu.ol1y .ppn)iCh~.Kb OI""' .t the midline wllne tbey fu,;e.Conl;>(mu , l body ~ion and proc~. in a ~phalic(.n_rl
.nd ..00.1 ( posl~iorl d ire<:tlon. T1le fold. ... m. in le mpor~rlly open ~l the cr. ni,1 and eaud.ll ends fo rming II><
anlerior and poster ior ""uropo res. Tho.., close during

fig. l .UDe

t ..... '"'... oIthe _

CIiniaIApplication

.. ~ .

--,

The obs<1V.1ion t!wl wou nds a1 without suning before
birtlllw proIIided an idNl oil lioo for COIRCIing malforma.
tions such oK • deft ~p .nd p.l1.lte. l~ng dcv i= ~
eflo1bl<'to COIle<1 nwlfonn.riono pren.t.lIy In
utero. Such operaliono . ... pe,fo"" ed near l he lime of bin I\.
Feral wou nd . ..... 1wi thout . ny InfL.>mma tion in l he pl.....-a
or t ylokinin, . which ini ti'l~ epit llcliali"alion.

''''llNR'


8

I Develop,ment andMaturotion o[,,.,,,Cro
'""o,;o,,'o,,,'o,,,,"'
,,;'oo"-

the foun h week. which SigMls the esta l>lishment of the
nervous system. Upon closure of the neural tUbe. a
unique population of cells known as "neural crest" cells
separate from the crest oft he folds (Fig, 1.13). These cells
immediately l>egin to migrat e ventrally olong the later al
wolls of the neural t"be, This is especially apparent in
th e head and neck region (Fig. 1.14). Neural crest cell<
give rise to a variety of differen t ceils that form compo nents of many tissues, such as the sensory ganglia. sympathetic neurons. Schwann cells. pigmen t cells. lep_
tomen inges, and cal'tilage of the phal'yngeal arches. They
also contl'ibute to the embryonic connective tissue of the

facial region, which includes dental tiSsues such a.' pUlp,
dentin. and cementum. Although the nemal CreSt tissues
al'ise from neural ectode rm, they exhibit propenies of
mesenchyme, As a re, ult, the tissue they form is called
"eclOmesenchyme." Growth and differentiatio n of the
neu ral tube begIns anteriorly. By the fourth week the
neural tobe has formed three primary vesicles: forebrain, midbrain, and hindbra in or prosencepholon, mesencephalon, and rhoml>encephalon. Secondary vesicles
rapidly develop from these primary vesicles (Fig, 1.15).
" lateral view of the developing broin is seen dt the
third, founh. fifth. and sixth week (Fig. 1.16). The brain
enlarges rapidly, bending anteriorly and expand ing laterally. The cranial nerves grow downwo rd from the laterai nellral tube and floor of the ora in, early enough to be
included in the organization of the developing face.
neck. and lower booy tissues (Fig. 1.17). Growing evidence suggests th~t the molecular mechanism medi.t·
ing craniofacial morphogeoes;, is the , ome as the molecules that regulote pother system, in the M y.

'm'·'- ·OO

2

0 "000P ..1001

3

Me>er>cepl\alon

4
5

Metenceph alOO

Myelencep"alQrl

4

_

we.'"

.,.,
Fig, 1.16 Devetopm
Neur.1tube
Mooode rm

Fig. 1.17 Dellelopmom of the Gltr.cl.


c.

--""""
enera! Human On'e'opmenj__'

Development of the Gilst roint estin ill
System
The dNriopinl MU"'l t..... ~nd thO' g;lStroinl <"li1' .-l~ 10 ~och Ol!'tt'r. In ~ =~ betwffn I~ t\lI/O
~'" lUbes. tM somj~ IOrm .hm> of mufC~
from ~.......oenn (fiI.. 1. 19~ As th<" "",bfyo IJOW$ in
ImgtlI. llle .Ii....... t>ry aJUI Imgthen< .IS
This

un.>1 nltnds from lhe ~l pl.1~ 10 llle ~
pLI~. f «h 01 wIIidI will <>pm ro pt
.,u.

oM mf from l he ..,....... !My UlW1.
T1w next J«1I in *'e' opn.. m is llle apppu an« 01
~... QUlpouclliJlp l~f 1M pllTOi",eu"wl
tube. Cran iouudJ,lly. llle fin{ and s.eo:ond pouct'ots pn:>Yick the ~,athyRlid~ s, th<" tbyroid from the my..
~I duet. the lullp. the enl.uginz: am of 1M <10m~ IMr. ~Il~lkt'. md p;mcre"": IIIlm' ~~ ior1)
the urinary bWJder dcYI:lops (Figs. 1.1811. and 8 ~ ~
thyroid &Wnd ap po'a rs duri", thO' fourth - t from me
junct ion of (he body and 1>.1", of the' ronguo'. • nd
~s in rile midline of the neck. Nat the bib...... l
lung bod. d,rr.......,liate.rod mla,!:". but fillN wit h nuid rlwoy ",,.,.,i n no nfunction.>1 u ntil birth
whO'n ll!<'y innalC with ai r. The stomach d . ""lop1 ' "
loc.liz~ enl'fgt',ncnt of the anterior gut and gradually
develo ps a. a mix ing and digesti"" org an , The liver
grows r,tpid ly and by 6 wt"eks fu nclions in red bl""d cell
formMinn, th . conve" lon of g luCOse to glycog<'n, .nd
the , !ora g<' of nutritional elemcnlS, The pane",a, and its
prod uct, In,ulin, de .....lnp ••rly a nd by 20 ~ek, . re fu<\Ction.>1 in t he p rodoctinn of growth ho rmon e. later
becom ing impmidgut rot,,".nd push"" into th e um bilic.1 cord at 6
but b',r the 10t h ~k t he
h'" incru stfKie nlly ,.. ti u to .Uow ret um of t he gut. The m'dgul
form s the duodmu m, the rcma indc'r of the small inttst,...... nd the _ending mol Ir.nsvc= colon ollbe Iargoe
intesfi ...., TIlt de

Illo" nd deYriops in (onjwKtion w ith the gmitou"n.ary 'YSlftIl (fit. l t8~ The alinwat"ry ""nat iI filled with kuI
mc~ of shod ~heliaJ
Ia
_k<.

"""'""tM cIctwU.

body

" ~J

fIoJ. l_'.~of lhcGl tr.(I.lA)~·S .... (lII S_ _

,ur-

cd'"

Development of the M u~Lar System
Ttlc m U'IeU"'r sy;tcm iI composed of " risi'" from tho, mesoderm, In which lbe propcny 01
contr. culiry Ius been h ,gh ly _loped. On the basis of
01;(1_""-=t!r'UClU!"C " nd function. th"", {ypc'$ of m us-

cle, "re I'f'<'Ogni:ced (Fie. I.ZO): 1) . kel..",,1 mu$Clc.
. ttadlcd to "nd I'P'SpOIlSible fur moverTJCnt of ttw body
~lcIon : 2 ) smooth muoclc found ellar. lhe w"lI. of lhe hollow vi=r., d lKlS.• nd blood vcswls:

.nd 3) t...di.c mu<;(I"". foond on ly in t he h•• n: w.lt

~

Olnic" I AppflCation

Ovul" tion is , /DOOthly cydit rvcnt con lrolled b',r the
eno:Iocrinc ..-oetions ~ " nd progt'SIC'nIM. Ttlc owm
m.l lu!"C' ,,00 Is o;pcIltimplant . nd "" nourished in the ute rillt' w.11 7 &ys
fi>rt i lizal ion. The function or "'" roolf.KCj>I M " pill " i' to ma;nu ;n .n incrc. std level of progestero ne ,,00 "" UQg('Il IhJ.t w ill
prevent fo Uid e m.luratinn (of lhe ovum) or ovul. ti on.
Without the ovum prcgn~nC)l will not occur.

.ft...-


Sk~etal

Muscle

At Ihe end of 3 wee k5 the OOdy h. s """" pairs of
.he ,,"ur.1t ube, The 'Omil<"5'rl:
rrwses of tissue thill conlribu~ to
!he.axw skritul lis ..... mllSdr.•nd connrcrM
of
1M body _II. Iy the )5th 4Iy. 44 !Win of 50mires Mil
Iwlllor.Kic. rIVe lum b.1•• r".e s.u.L .nd tigln 10 to'll coc~ntd as $qffiffile

,iI_

cyge. ' , M=1e ""'" ." following th e $.Ime pall t'" g row from the somite, along the body wall and
(f ig. 1.Z0A~ TIlt fi rst occlpi t.1 an d tht la,t
fwe 10 !i<'Vm cocsomit.. COJIlnbutt ~ to the ~ntbr.1 column. I....
6crmis d 1M skin. mll5des of !he trunl<...., Iitnbs, .nd
SOI"M musdH of Ihe 0f0lKWl ~ (IC.. l2OC}.
.p~nd.ges

By 10 Wtth. lh t myobLo$lS(m usc'e (~I$) ~ mivated
and begin spccl. lj2ing imo elongated , mullinuclN ltd

muscle fibers (Figs. 1.2M and B), These fi t>ers divido into
group" <,pi mel\'1. which supply tbt dors.ll .uff~ of the
limbl. .nd ~ which supply Ibntnt,.1 p.>rts of

!he lImbs.lbey ilsosplillmo superi'"ocW.nddHp lq=
01 mllSdr. In eMIr ~nt. the mUKks follow the
>q1JWntill p,ot~ of ~ ",m~ but by the elglllll
\\o'ffk th iS p,ollffn dis.>ppta15 (Fi g. l 2OC ~

Smooth Muscle

:::=
Fog, IlO ( ~).
(C). O;I1_

~

oI, keIeI. 1rJ>.JKlr C81, Musdo types

;"t "", of '~"""' , I muK'-

wo"""'"'"

N. a ony eilr1y SfaJ" of ~l,
IIlfSEiochyrn.1J «lis «lnCmfTate 0fIlW>d 1M IPpit!lflw ~ nings
nlludI struetu~.os the IIJI lubf. Urogmlt>l dlKlS, ~nd
the 1.."Be ""$C\II~r c""nllfls. Tbo>sf I11f>fDChyrnil cells
arrange IbemSfI= in lOnes wh ere involllnt.,y mll\.C!f ,
(smooth ).", deuined to develop. and then k "lll lltn in
tllt di""'tion ~i r m ntrK tile powfr will be CXl'lted.
~ do:'vdoplna smooI h and ~rdi.K musclf <:fils ~'"
both ronuol lNl by the ~utonomi<: nnwus 'Y'h'm (Frg.
~;

Cilr d liK Muscle

-

D,

•

In tllt early Slolil'S of d ifferent iation. cardiac m uscle cells
are packed d l»t'ly tt>gether around 1M d"""laping hean
tubf and exhlbil no dri"lnl!<' plan or ~rranv'....... t (fig.
121 ~ .... the dc-.dopilll lissw is pulled inIo

~ 1M ctwnben nllhe lINn. lhe m~nds b«u.".,
IlloOrr ffgUl ~r in ~ffil ngm>mt until they aplH'~r 10 conli nue in • g' IIff~1 pa rallel f~shion. The "'Sfcharact.".iSfi<
fealur. to ap pear in lhe d..... lopme lll of card iac m u, d .
are the intercalated discs (Fig. 1.20 8~ Electron microscopl' Slud ics have shown the", tr~ ns.....rse ma r1be hiShIY modiflC'd cell bou ndaries. Myofibri ls on either
sOdf of the d isc an. atuchfd in ...c1l a rna""", that tbO'ir
cootraaile ~ c~n function lllftlUlh the int....roon
of mony crUs.


I Geflf'rol Human ~Iop'!'.~n!

11

Developme nt of t he Heart and
glood- vescular System
Th~ d~IOl'i.., .....bryo 0' '''''lIS i. att~ 10 1M pLid....,lopmml 10 b«omc 1M umbilical cord. Bodl .~ •

.IJ mol Wl"IOOIS bloo::d ~ form in thi s cord . nd catTY
~ dio'dd~ _ q from tM r rnbfyo 10 1M placml.O
and 0ICYZ'!"1 and nunirion 10 tM <'111br)o Of ~ (fi:&.
1 .n ~ Blood fIowIlO 1M ~ d uring tM fi f'll 2 ~
IIIrou&:h lllt viM liM cimdotoly systm1. ....id1 arrlts
""'rilion ' rom 1M )fOlk ..c 10 tM ....m. OUrinlt.... ",in!
~ 1M " mbolic..1l ctrculation t al" muctl ~ prtwllrnl in \own anima ls th.1n in tilt
hUJIWL AI. 1M ~nd of 1M first month. thr rmbryomc:
hr.n btgins to boNL OXwn is then lran"""ntd from
Ihr mate1"l\;ll capillaries '" m r pl;ocenU aem.. a eembr.... fql.Ir.li.., rh~ twO sysceros. TIlt fcot.1 ~ blood

Cl'lls a... . ... sllown ,n f,$"'" 1.22. In tho um bilical cord. a ~n
r.II,N than . n .ntry carritn. 1 M.rt. x ner m is blood circulat.... throughout the
ferus. it is then '. umb ilical arte , i to lhe
placenta (f ig. 1 .22~ At bi, "' the lun gS ...place t pla centa. and the pulmonary a'te, i", will th on cond llCt
oxygonattd blood to the newbor n's hea,t.
l1le pld,'~nt. f""ctiom as . nutritional link between
m(}{ l1~r and f~U1 1 (Fig. 1.23) dnd serves as . slo,a ge ban k
of nutr ilio n and a sltr of rxch ange of oxygen and carbo n
dioxide. Howeve,. there i, no direct contact of the blood
ole~nts in the pl.lcenta . s bot h s)"Stems a.... separated
by • membr. .... The "",!(or"",1 blood 11""" r rrl'CliV<'ly
~ ui e Was\"e prodllClS that cross the placental
membr......

... .".
,, ~ . ,

-

..,'

t

fig. 1.2)I'\o
",.-0,

~ . " , . . . . . 00

12

I ~n t on"'-

_

no. nnbryonic hem

;R1li.1lly o:lI'vrlopo> by fusion of !WOO
........1> into" ~ blood ~ Iorntinz tht m clod . 'klII
hun tube. In " wries of $R'p$ { F;g. l14 ~ thiJ ~
~ lIlId bmds on ' tsel f. " ,.;I its tisst>ediffe-nml:llIlft.
Then " dwmbn-s. sepu. .uad """-" ~I"" which
tM
"uto from r.........tricll!s. In "'" eonbryonic hem. blood
colle<:fs in tht right " tn um ~ mosf 01
blood
1>'=
into rhe k1t " ,rium tftrougft ~ ftlf"mm ov"I• .
BIoocl t ..... PlIsstS to the ltft ""ntrick wft.~ It ii
pum ped thro~""t the body by the aoort. (Fig. 125"' ),
Very litlle ~lood p.l$ 5I!' f, om the right m i" m 10Ihe r ight
vennicle. where it 15 pumpe d to the dc Vl!lop ing \ungi .
Blood byp ass. , lh. lun gs. pass jng t hro ugh the duct u'
. , te rio, ,,, to lh. "ona (Fig. 1.25A). Th. fetal hea l't 15
at iVl!ly larger . Lld l><'.IS mo... rap idly tha n t he po'l natal

hea rt. ,ince it carries blm to lh. bod y a nd thr pl. cen ·

'.'p""u.

t'"

rer-

"

~irt ll. = r .1 "",jor clunges OCUlr
1258~ When lht inf.nt Ute. it<; fim

AI.

10 lite he.rt (FII
br-." h the lungs
inllat• • ,.;1 . """I sUp 01 muscle slide.
for. .... n
""ale. whiclt is t he openif\l bt1 .. . . n ,.... right . nd Itft
. 1Ti.I. This ctosun: !oms .n "'" blood in the nV't arrium
in to tht righl ..... tricle .,.;1 to t'" lung<. no. blood is
IhI':II rerumeclto lht Id'I: " m um from the IUIlC' by the

""",m.

pu l"""""Y "";ns. After biftb. lhe dUCIus lIItmostts
10 ~ whidt ~ blood from P""i'"
di fa"tly from tile pull1lOl'1MY • .--ies to the aooru (fi&.
I.2SB ~ Thesl!'ctw>&ts lll: ~i rth .r-. vi.., l to prevent .1llu.

b.>by" (oxyzen rlriicienl~ As . mull. postn..>Wly lOU lhe
blood is ~rod befor-. be,ng ci",,,la..d to lho! .n li~

besins

"",.

,

Skeleta l Development

FiSI . 1.25 '" ",,","t, 1hea' t. Both o'j'genolled . nd """""l'9<'oa..d blood ,01·
I...:~ In tho rigM 'tri"", t o ' ho riqllt "" ntrJ<1< , nO mixed blood pumped to
t he body. Bl'ot hM to the I,"'g'. ft retu"" 0<)"
~!<'d to the loftmia ood ""'" the loft ~ and;o pumped to tho!

...

_ ride.

The skeletal dnd . rt icu la r ' y, ,,, m, de ve lo p from rhe
""" "dermal somile s. w h ich diffe re nt iat. inlo s<: lc rolOme, and de rOOOlllyotomes. The s<:leroto""" wi ll form
u rti lagc. bone, .nd ligaments( FiJ, 1.26). 'ieIIc..1type s of

_ CliniQl Appliuldon

-,

an. dQm.>oc dwniIe.l birth is the n.nsfOnNl:ion

from the doSI!d $ySlI!m cI the he.on to m open one .
~ birtlt thii is olCCOrTIPllshed by utilizinz blood
lkrw from lht plllCent> , nil conductillJl " 10 " nil
th "",gh the ... art. fhen circul.ling it 10 Ihr ~" of
th~ body. At birth ' he hedrt forttS the blood into lhe
lu"&,, where ;1 is oqge ""ted. The blood Is lhen
Tetutn<>d 10 t he
an d pu mped thr""gh<>u t lhe

"'"

"",n


1General Human Ckwlopment

U f1,lage d~IOtlIO supply til<' bOOys ~<. Hy" line
<" rt, lap' forms throughout til<' ~mlxyonic; md f~lil body
md i5 III<' mo$l promin~nl type. H........,.....,. ri.o"i~ u m·
Loge forms to the ~ars " nd Iibmus GlIrti~ form:!; in the
..,.,,1 minot\. !lone lim ~Iop$ ~ ""'" ty l"'S of ronntnd r,,1 Of
inum>tmbr"nous {r ,!,- 1.27 md l.2l1~

Tht first sttItaln IOdt¥riop in III<' <'mbryo is c~
01 " PPCMl rh roughoul: lht body: in t!It ni.ol slbHt of !he cra nium. "rid t ilt ~ (~ 127~
Clrtilagt ceus fil"Sl ap lI""r dufinz" the lOultII iRd fifth
-..t. " rid GlIrtilagt lri:< ""'" aplI"" rs throtogtw:>ut the
body. , ,,nil. provi

Ihe sktltt.ol sttmgth " rid form:!;
a .... lm whtrt bonot eens will bier fOnll boJ>to. L.1~
nUlritnl blood \'tssds mtn tho' UrtibgtS. "Ad boot
form. 'n",,,11y ,n lloe sh.lfu and .. ~ in til<' proxim.>1" Ad
di sr" l hcad. of Tilt l>onts (Fig. 12' B~ By lh~ 20fh wttk.
of lhe u Ttilage in III<' body.
bone ha. rtplaetd _
(mila,. w ill ulTi mately t.. limitNI lOth e coYenng: or lh e
hea'h or long !>ones. lilt Odsat septum. th~ trach. a, and
sped ailled cart ilages will provide support I", th e ear s
(. lostic) ~nd the , pll1dl column , ( fi b ro " . ~

.............'" Bono FgrmIIi!!!l

Bon"
Booe m ay endoc hondral me" " s, or frans lonnatiOtisRtg.l,...,.ltonT skeleton wil1 l\.tw u... same "Pl"'" r"l>f" nct ion whel htr tomp.a!.paCt is ("nctllou. or spongy_The _Iopi", $kuD i, "
d.1ssi< example is iI ron t" i". boIh """"",,""""'us bone.
whic;h COOo'tn lloebr"in "Ad ~. "nc! r.mi~
function in lY"C1ltorI1 '" support md prolNt the br"; n
.and f.Ioct. T1Ils wil be " esaibed in detail in Chap:er 4~ 128 .,." l he iniml formation of rnttnbr"nous
bone (lIM bontsl wIlich forms in rooneail't tissue. is

weU ... " ~ ¥t.1I 01artilagt W t i5 modified
by tndochondril bunt lOrm.1tion.

Morphologic Ch.mges d uring Prenatal
Development
Embryos inert... in size first by tell multiplic;~lion. St(.
ond by I'owlh in ;nTHeell ul~r depo sition. ~ n d Third
lhrough " mod iflc~lion of $;Ime w ll <i, •. Fre>m T~ {(on il.
i;red ovum ll~1l" until birth , th e hum.o in<,.."lOS In
length from l«l llll io more lh~n 50 em , .ncl in ......ighl

8

-.

12 18 20

2. :Ie

fig . 1.2~ I"" re. '" in weighl and "'"9t h ofl>ody.

"

13


from • few II'\IUilJams lU _

tIwllOOO J in appnsUmaldy 266 days (fie. 1.29) Th.... fnKD fntIIizac"", 10
tnnh the body ;~...,. ;n me about • million rimes.

The MIbryonk period i< 0 "'" 01 rapid IJIJINth and differentialion 01 «'lIs. Ofj\ans, . nd olJoln sy>~m .. All INjor
~aru. ", are es l. blilhed duri "i Ih,s li"",. (;rowth may be
intemi.ia!. involving an inc",ase in bu l ~ wil hin a d lS" e
or or&dn. or appoliliondl. involving enlargement by surra,.., deposilion of ' i..ue. lo,erstitial growth is a characto:ri' tk '" soft !iss ue. where•• appositiooal growtll is a
char.lCtm sric 01 mineraUZl'd tiSSUl'•• uch .. I>c>den ral h.ord tissues. ..... ex«p(ioll is canilage. a hard lis.... l:Iw.l illClUlft in me by both ;"'e"'''''1 .nd appositional JI'OWIft. MucIt 01 the inmsIitial Jf'O""Ilt occvn
dllti ng .....d Opl1lell( when !his ttssue is >Oft Oft in a . . .
mi.......hZl'd state. fol mal nnw e~ cd! Of cell IJ'OUP
dO'J>O'i ~ a _ rix utMlnd !be cell .
Diffe....t .. l ,.-th is ....... Iial ,o prod uce cba"itS in
sil e . nd !hope 01 dilfE.renl body parts, An ~mple
would be the chango in proportion of hoad . i, . by the
end of the emhry{mic period a, 8 wee••. Du. illg the f. t ~ 1
period from eight weeks to bi. th the' body inc"'alel In
Ii..., at a (d' e :reate r lilan lhe head, The he'ad "'prf""ms
one-ha lf or rhe IOUl body al 1 moot .... one--tbi, d lIt ~
months, and on~fourth .n binl\{ fis- \30 1During !he Ilm 2 prepayl mont ... rhe'hea" devdops.
blood bel>ftS to cimllate. the body etong;o.... and the
human fan! d""elop> (fIe. Un fol lhund otibt Itlird
rnonrh ibt Uppe1" limbs MaC!l altn&th pibt nest 01 tile body. By the end 01 the fourth mont ll.
ossilk.nion cenren ~ made their 'Pllea",,,,,, in most
01 rhe' bon.. and individtul diffe<~ become .pp;ll_
en" Ar lhe end oflhe fifth moolh rhe fi1us is ~boul t lll'
leng'h of . fUII-l:erm ~t~S ; however It weigh, about 500
g. which is one· s;xth it' birth weight, By the end of the
i;xth month the Iaceis infant-like. • lttlO ~ g h the skin Is
wrinkled because of irs rdpid growth and Ia<~ '" developing adipose titsue. By lhe' end or Itle """,nth monrh.
bowevet". ibt fetus ""' Moidoped suJ:>cut.'Ineou f.il
..hmi nali n: !be Ibn wri nkles.. Ai this time. Itle tJ"lids

no ~ fIMd lOi"IIIn. Body lDO¥O'IIX'fIIS now
bO'comO' p~ moR 1>I:;Ilia. . .. Mow...... ollhe
~ j.lw bqins as e>rIy" !lie ellhlh """,k. but SUCh "
minor """"""leI IlllOf leI, by the rrKKlie'r. Ann and
flexing begins as ,loin.. matUT"f. and rhese JnOW1I>O'IIt•
. ... quite notice"ble to the morhO'r. Duling the ~th lInd
ninth monlhs. lwir dnd fingernail. IIl< .... se in length and
the body becomes mO'" plump. In the late ptenJt.1
month, the body ;ncrea... , in weight unti l the fetu,
rf a""". abou t 3.2 ~g. lhe ave•• ge ~ghr of an inf. nt.,
bi,,1\.

=

rOJ. 1.31 0r\9n oIltIo _1'Il>Ce'Il.

Clin ica l App licat io n

le,

....,

All ",II. h.o~ . limited lifi1inw, The life ....n of. w h j~ blood
cell is only • f!'W hours 1<> • f!'W doY5- On ~ 0' ,," h.olld. "'"
blood «'lh live .pprox:i.... 'ely 120 .s.y,.nd . re lIltn dmruycod
~ ~ Cells 01 the slin. IW•. OJ ... il. I'ftleW ;r< tbty
Iomet ~ '!UI:>UIhOUt h~. O!tler<:rib in the bcldy do nat nor....I/y mww . fter m.uurity unless tbty h.ow btftt inj urnl,
such .. «'lis oIlhe livr •. kidney1. and Ihymid gland.; mm
they may ~'l:e !O <OfI'lt elll:enl NefWS have.n exll"1.'ITIeIy limi led eap.>

.e placed.

=

I


Birth
Partu rition or Id oor begins with m uscular ,ontraction.
when U", fetus h;n atl.lin..d t he PfOl)<'t posillo n deep in
the privis. ~ ilmniQ(ic "uid is liqUC'<'zed inm the lhlD
JW1 of the chorion ~ ~ 1M Ulniroe rnvix. TIns
KtJ .as the pno!imilWY diLator of ,.... arvicoll (,In.ol. As
conlT-'ions btco"" 11lO~ JIO"IlfffuI and fmlu,,"l. ,....
investilQl memt>ralles rupeur. and t he infam i. frfffrom the fct.l enve l0Jle. The am niOlic fluid S' dr" to flow
from the moIher, w hictl lubricalcs lhe birth unal (Ai1.l2~ Ilo'<-~ r.... ~ of binD uSIIol11y 1.&5 ..........ll
boun. it is imporunt th.ol the ploanLl ........,"" attMiwd
!O the ..-us. If the retus ~ CIIt off ~ rrom
its r,..I1.......1 ...socio.tioJ!s. It could not survrw me proIonge
Comhined contractions of smOOlh muscle in the
uterus, . ide d by contracHons of Ihe skelelal muscle' In
!be ilbdomM, Jim-ally sq.....,... llie r.,' us ;nlO ~ slowly
di l~ing CftViuI Cil"'" WJw>n dU~ion is ...rr~It. the
krus is ~ out "'!be u.......... This is tilt fine ~ of
labor. ~ Iirv, The fetus ...."'ins through the ~.l c....1 ~
prompt!)' th rough ' M v.S i.... an d ·p~nI5· Its, l'. The
vulval orifice dlla'es rapid ly, and whe n the head passes

tho OUt~ l ho ...,t or l ho body emerges ""idly. With
dlnilftnal co"neui"OI' .are ~ted ~ fer
lim
Iinw. the .... boI" sublim inindividual .

I""

Approximately 15 10 20 minute. after the binh of th e
baby. me uteruS begiru ano ther serie' or ron tracrio n,
which 'Ie"'" to loosen and expel tho pL>cenU ..nd . mni ·
otic 1l'ffi""R1. This entire min Is o ereOl ~ 1<1 ;IS tile
This abrupt: shrddinS of tisutefus ilMl""" contr.. cru,n< of tho uteru s /fllll,m ize blood loss by c0mpressing the ruprured ves..,), . whi ch tl>ereby f""Hitam
"'I"ir or tbt: uteri "" lininl similar to !he one thilt occurs
..rrer mensrnutlon.

-.fIerbinh..

The prucns of birth <>mIrs.about 9 10 !l5 months..ttft'
COJlCeptiUR- A romplete envio"Ol\ll'lefllaJ trinsformalion

I

I

takes pl

warm. dark , an d relatively quiet environme nt. having
been sU ~rged in nuid at a body te mpe rature or l 7 ' C,
intO i lighted , noisy environmenl apptO;rooIer. in which it mUSl support il$elf by breathi"l olir
tllrough its - . . Iun:&s iIld tiVl' indepeilde"dy. Th.... it
birth the jnWl[ must .lIfYMo i number or pItysioloJX:
changes, such i . Ihe in. piration of air 1I"""gll its Junp,
thrO\lg h the lungs, ora l ft'l'd ing, use or tne gastroin testi nal tract. utilizing ...ns>! organs of sighl, sou nd, and
.....11--..11 of which create new and complex r.eliop.

Rg.I .32_


16

I Dewlopffi€nt and Maturation of the Cranio(adal Region

Abnormal Developmen t

1
1 2 3 45e7 8

Emb ry<>ni<

I

(wk51

F. ..I

The causes of congenital malformatio n' m.y be hered i_
tary .ndlm environmental (genetic aLld epigt'netk~ The
majority of congenital defecl< are the result of inter~(­
tion belween heredit~ry .n d environmen lal f.lClOr,
",~ur rin g at a specific time of developmenl. 1l was
recent lyreported Ih3{ SHH protein pres~ nce is ne.;e ,sary
for growth of the fronton,ls~1 prom inence (, t.lgo 23
chick). Sign3ling from this protein i' critical 10 nor mal
development of Ihe mid .lnd upper face.
Beyond prenat.ll examination' and p;lren t~ 1 counseling.
not much c~n be done to reduce hereditary h3z,lrdS in
human, . Re<."nt experiment' are being directed IOward
ailering the effects of abnonn al genet ic endowment
through changes In Ihe environment ' uch os reduction J nd dieta ry changes.
Our increased knowledge of noxious envil'On menti1 1
. genlS (Ieratogen,) and the time of their maximum
effects On fetal development is of great impo rlance in
the understanding ~ n d prevention of weeks). At that lime d3ffiJge ,,",y be compensatethe remaining c. Us that have not yet be<;ome committeor differentialed. The embryonic period (third Ihrough
the eighth week ) is the most critical time r>criod becau,e
il is Ihe period of differenti~tioI1 of tissue< and organ,. At
Ihi' time. teratogen ic agents may be highly effective and
re,,,h in numerous malforma tions. Dliring the fetal period (end of eighth wee k unlil birth) susceptibility to teratogens rapidly decline, and mJy cause only minor
defects (Fig. i.m .

Hered itar y Causes of Conge nita l

Malformations
Hereditary callses of congenital malformations can be
.1l!ribuled to either chromoso m.l Or genelic abnormalities.

Chromo so mal Abn o rma litie s
Many corij,,,,nitJ Idefects are now known to be the re, ult
of an abnormal number of chromosomes. The abnormality in number is expressed as either J decre.lse or


"
;nrn,_ in

I ~ nonn;Il n u_
cI d\tOfnMDInn (46 in
euploidy. A de<:rN~ In _
cbro!TlOS011l".
moOO$Omy (4 5 chTOO'lOSOlTles). is uSlJollly Jel:hal. Turner
synd rome (XOJ is noI let hal. An increase in on e or more
chromo wmes is (e rotoge nic dnd res ults in co nge nitdl
"", Ifomanons. TIle extra ch romosome nuy be an au to"""" or a so; ch~rtIC'. If an ""tra cbrornosomo.o
membe1" IS ponmt. a condition known as trisomy dwndlllml! (Figs. U4 and 1.35). In th is condition ~
IIIoOcell< of I~ affected Ind ivid lJoll. wh ich I'\'s ,dts in tIM> cells
e<>m~i ni n 8 47 ctlro mOSOTI!<':l each. The nulfoTll\ilhon is
ch"rd(l..i,ed by ment~1 rer.n ddt ion. upward slal1ling of
the JMlpeb<.1 fissures. a na t "..",1 bridge. a nd . r,,,urepro trudillj roog... (nuaoglos lia). ....... ~r """mpl e of
chrnmosomal abnormali ty is Kleinfdter syndrnme.
Th. ... a... """,ral rypes. one is the XXV indicoIri1\l an

mcr._ in I~ fmWe 1ft d\romosomI' • The.....1eis ull
of RaW,... has defkkm l"Rel d~lopmoenl. and
requires addiliONI ~ to funchon norm.>lly_
OCh.. more ..riom a nd sevn. fon m of fh is condilion
a re t he XXXV a nd XXXXY syndromes.

00'"

ltu m ~ n s ~

I'll;
1 2

U

11U&

3

4 5

J''lU' al:t .P,

.. ..... . .... .. .
e

7 69 1011 12

' 314 15
l tl20

1eUj'

2122

---

JO(

X ffi, - ~

u.......,.,._

Blea kage " ""

-

_ _ ,,,,

xo

--

_.-

",
ii-II

8<0_"".

_ ~ on

I.

f+o
•
a_,..",.

""lI

Trisomy z t

Down's Syndrome

Genetic Abnormalities
Gmes a re oegrnems of the OI'IA elwin fur -.:I infoanor,,". Abnorm.>l dewlopment may be tile "",,II of
""preuion of d.feai~ ~ w hicllmay be domi"",nl
o r ,.,,<. ssi...... A d om;na nf geM expre. ses itself wtlcth.r it
is presen t on on. me mbe r of th e pair of homologous
d Ht>m<>some> (he leroZygouS) or on bot h pa irs (ho mozygous). A ~siw sene exp~ 1""lf only w hen il is
presenl on bOIh members duornosomes. (fiI. 1.J6). no. followi ng al>nolm.lh lie's
.r• ..umple> of ~lowm.ol domi"..nt ~ ~
cepb.olosyndaclyly (F"l&-1.37), achondropl;lsia, deidu<, ....
ni.>I dysoslosis. mmdibuloEaci.oI
--

","1 • •0

,,".._ p

'i'
Ai ,

-

P

" ",w,g' y

P

d

P

PIP

Pip

Pip

pip

-I

'.

A