Clinical Embryology of the Eye - Dr Pranesh

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A ‘Teach to Reach’ Initiative

CLINICAL EMBRYOLOGY OF THE EYE An Illustrated Manual 1st Edition Dr Pranesh Medical Officer Aravind Eye Hospital and PG Institute of Ophthalmology Coimbatore


PREFACE Embryology of eye is a difficult topic to master due to the obscure understanding of general principles and lack of application of the learned concepts in our routine practice. This handwritten manual aims to bridge the knowledge gaps & missing links - thereby presenting itself as a Complete Course on Ocular Embryology from Genes to Clinics. Highlights : ① Profusely illustrated with colourful diagrams and clinical photographs ② Flowcharts to aid understanding of complex derivatives ③ Every detail on individual structure is accompanied by relevant applied aspects ④ Must read for residents, practicing ophthalmologists and paediatricians


CONTENTS 1. General Embryology - Overview Basics 2. Ocular Embryology - Overview 3. Brief summary of Derivatives 4. Development of specific Ocular structures a) Optic Nerve b) Retina c) Retinal Vasculature d) Hyaloid Vasculature e) Vitreous f) Sclera & Choroid g) Iris & Ciliary Body b) Lens i) Cornea j) Angle of Anterior chamber k) Lids & Adnexa

with relevant

clinical aspects

5. Genetics - in Brief + Discussion on Coloboma 6. Big Picture + Summary repeated 7. References


GENERAL EMBRYOLOGY 3

Germinal Layers

I

b

Ectoderm t Surface

Endoderm

Mesoderm

Neuro

4 Neural

deum

Ectoderm

t

g

I No contributionto

oculardevelop

Mesenchyme

Note Contributes to Eye Development

Mesenchyme

Nut Mesoderm

NCC's contribution

Mesodermal Mesenchyme contribution

So for all practical purposes here

Ncc

Mesenchym


3 Layers formed

finishesKydd wk

0


Gastrulation T

Neurulation

formationof3germindlayes

Formationof neural

tube

cranial a pole cross

section

caifdalpole


Neuralcrest

T

Neuro

ectoderm

from neuro ectoderm

Neurulation


03

c

Neural Tube 3 Vesiclesformation

is


OCULAR Day22

EMBRYOLOGY

lsteventin eye develop


Neuro ectoderm

Tencephalon

Thickening of surface ectoderm


dotes

by 7thwk

OpticCup

if not closed

Inner layer Outer Layer

Coloboma

NeurosensoryRetina RetinalPigment Epithelium


migrating

Ncc x

cells Ncc




SUMMARY

must know



Optic

Nerve

Neuro ectoderm

Hyaloid

vessels

Central

Retinal Hall


Congenital OpticDisc Anomalies Congenital oD Pit

focal excavation

on

0N Head

Examine in

Discserous central

petinopMM

I

Serious detachment

If

1

pit


OD Dusen

focal collections of axonal metabolic products

Buried

dmsen

Pseudo papilledema

calcified deposits within ONH


Anomaly variant of Glory Morning oboma OD lol

Axial Coloboma

Geneinvolved PAX6 M

c systemic

Association

CNS disorders associated

FrontoNasal Dysplasia Neuroimaging required

Large disc

tunnel shaped excavation Ring of

Chorioretinaldisturbance

spokes of wheel pattern emerging vessels

of radially

discussed in the coloboma OD Details of

Last section of the manual


Myelinated Nervefibres Medullated Nerve fibres

progression

Lamina Cribwsa of Sdera CLA

of

starts from optic tract ends Lc myelination

t

if Oligodendrocytes migrate

into intraocular area

Abnormal myelination of Ganglion cell Axons b'yond LC

I


Optic N Hypoplasia

fed Nerve

f

snes

Uk

Squint

Bk

Nystagmus

I

de Morsier syndrome septo optic dysplasia7

7

Absent Corpus Callosum Septum Pellucidum

Bk on Hypoplasia Hypopituitarism


Reti na

RPE

n Neuro

sensory retina

inn

Edmond

d L

Marginalzone

TransientLayer of Chievitz


Macularitoveal Development Foreal maturation completes

4thmonth

Fixation

Reflex

I

if impaired develops

Nystagmus

Albinism eg.in


Retinal Vasculature

t

I

2nd

Temporal Retina

fully

Of

vascularised

by

I month after birth

1st

Nasal retina

fully Vascularised

by 8thmonth of GA

H i Incomplete Vascularisation of Retina in Preterm infants Vascularisation occurs in Low O2 tension in utero


RETINOPATHY of PREMATURITY

n't

In Preterm infants

02supplementation given for

lung

immaturity

902Tension

1

Growth of Peripheral Retinal Vesselsout off Retina thinks no need for vessels dueb ROD Oz removed

Ischemic response

t Leahy 4

new vessels

abnormal vessel production

fibrovascular

Retinopathy of Prematurity prop

Tissues


Retinal Vascular Anomalies


familial Exudative VitteoRetinopathy

I

1119 to

Rop

Tt failure of Xascularisation

of Temporal Retina

Screen the relatives of PE E FEUR


Hyaloid Vasculature

portionof

pinkaneural Hyaloid vessels

t ya

central

Retinal A'eV

aeagyeof

Tunica Vasculosa Lenh's

yfgawdue.se

TUL

3 components AnteriorVascular Capsule

Ant pupillary membrane Capsulopupillary portion

PosteriorVascularCapsule

Post Pupillarymembrane

refresses in Thrimestv Regressed PrimaryVitreous

t

Cloquet's Canal x

Details below


Persisting pupillary Membran

Mittendorf

Dot BergMeister papilla


t

ft

Bergmeister papilla

Mittendorf Persistent

fetalVasculature Retrolentalmass

persistent

HyaloidArtery


Vitreous


Vitreous Development t.de Pnimary

PrimiliveSeconday Definite.ve

Tertiary

ViFeousPwpev From Mesenchyme

of Ncc

From NeuroEctoderm

Surface Ectoderm

1

month

Vascular whenzolineous

fills cavity it

becomes Cloquet's Canal

2ndmonth

AVascular 1

fills the cavity fwmjtfyafoyt.es

7mm Neuro

Ectoderm

374

month

Becomes

Vitreous Basee

Ciliary2onules


Persistent Hypoplastic PrimaryVitreous

Persistent Fetal Vasculature

t

t

t

Persistent Posterior

Persistent Anterior Fetal Vasculature t Reholental fibrovascular Mass

Fetal Vasculature

t

Retinal Detachment

LEUCOCORIA 11

DifferentialDiagnosis Retinoblastoma

Persistent 7daL

Rop Retinal Dysplasia

congenital Cataract

Toxocara Endophthalmitis

Vasculature

Goat's disease Coloboma Choroid

ODisc



Persistent

fetal

Vasculature

Persistent Anterior Fetal Vasculature


Scleras choroid

Ncc

continues Anteninly

sclera choroid

Substantia

cornea

propria of

Ciliary Body

Posteriorly

Dura

Pia Arachnoid


SCLERA

T Tempyalsdera t

from Mesoderm mesenchyme

hotherparkofsdera

I from NCC Mesenchyme


Iris ciliary Body

Outerlayer of optic

up

Inner

layer of opticCup

In's D Mff

fromNeuwectoderm

Muscleof CB Ciliarymuscle

from NCC


Vascular mesenchyme Pupillary membrane

optic Cupmargin

Neuroectoderm

cm a ciliary muscle

CB Ciliary Body

Tm Trabecular Mesh SS

Iris

J Retina

scleralspur


schlemm'scanal 0

Cp Ciliary Processes Posterior Non Pigment

U

Epithelium

of developing in's

Attains melanin pigment Melanogenesis

Ut Becoming Posterior Pigmented Iris Epithelium of


Melanocytes

Ncc derived

FT

t

Neuwedndermal derived

t

choroid skinehair

RPE

f Race related

Epithelium't Irisa ciliary body

to

pigmented in all races

If

affected melanin production

d ALBINISM

Oaelocutaneous

Ocular


Oculocutaneous Albinism Tyrosinase negative complete til Not capable of producing melanin

Ilusinase Incomplete

Hariable Melanin production


c

Let us review

Iris developmen

again

PAX 6 gene mutation

Aniridia Autosomal Dominant

BIL condition

not complete absence of

misnomer

Abnormal Iris seen

as a

stump

of

hypercellular stroma

Leads to malformed outflow system

syndrome associated

L WAGR

syndrome

WT mutation

iris

Glaucoma 75 t

WIM'sTumor Aniridia abnormalities

Genitourinary Retarded mental status


Do 456 Abdomen for all cases of sporadic Aniridia to detect Wim's Tumor

Partial Aniridia

Total Aniridia


Associated features

of Aniridia

calaraff

701gal subluxation

Assoc Limbalstem

cell deficiency

Hypoplasia

Poor'Exation to Nystagmus


Lens

f

formed in 4th7kWh

Surface Ectoderm

Affected in

Rubella in 1sttrimester y

congenital

primam lens fibres

cataract

f

Equatorial LensBow

Embryonic

Nucleus


Lens Vesicle

d

v

Anterior epithelium

posterior

1

epithelium

t

equatortorms

secondary

1

Lensfibres

SLF

elongates

loses

formprimaylensmoki fibres

fetal Nucleus Infantile Nucleus Adult Nucleus Coney

1 Embryonic Nucleus H

central core

i oldestfibres

SLF

grows anteriorly posteriorly

Feet t

y sutures

anteriorly straight'Y posteriorly

suture dotted area

inverted1

iii

i i


CONGENITAL CATARACT

t

I

I

43rd

43rd

H

y

Assoc I

Notassoci systemicillness

t

Nonsyndromic

Metabolic disorder

Hereditary

Intrauterine Infections

1

Syndromes

Human

gamma Erystallins intens

tens proteins Genes encoding crystalline mutations 1

Cataract duets

I

protein misfolding


Assoc E l

t Metabolic disorders

Galactosemia

Intrauterine Infections

Syndromes

GPUT enzyme deficiency

oil droplet cataract

Lowe syndrome

t

Galactose 1 Phosphate

Luridyltransferase

Oculocerebro renal syndrome

XLR

Fabry disease Mannosidosis

deficiency a mannosidase


Assoc E l

EitEfinne syndromes

Moffat

b

TORCH Toxoplasma

es

syphilis Herpes

RIbeyatcytomg.gg


Congenital

Rubella Syndrome

Gregg's syndrome

H Classic Triad

Dense Nu ear cataract

Rubell

Retinopathy


Congenital syphilis saddle

shaped Note

Clutton's Joints

SabreTibia

notched smallteeth Hutchison's

Teeth

Interstitial

keratitis 1

Sensorineural

Hearing

Loss

HUTCHISON'sTRIAD


Congenital Toxoplasmosis SABIN's TETRAD

Cartwheel

Madison

Intracranial

calcification

Mental Retardation

Hydrocephalus

microcephaly


Syndromes t Downs

Trisomy21

t Edwards

Trisomy18

t

Patan

Trisomy 13


Down's syndrome congenital cataract

flat nasal bridge Brushfield spots

1

Y

focal areas of stromal

Tissue Hyperplasia Upslanting palpebral fissure epicanthal folds

Got Hypermetropia

error

Mc

Refractory

M

Typeof Astigmatism

c

M c Typeof strabismus

NLD obstruction

Oblique

Esotropia

common



Defect information of Lenscapsule

H

Lenticonus

Anterior

1 Assoc

c

ALPORT's SYNDROME

Posterior

t Assoc E

Lowe's

SYNDROME


t microspherophahia He

smaller diameter

t microphatia

shatter diameter f in Lowe's

spherical

A

Risk of Pupillary Block Angle

closure

Weil Marchasani Marfan's Hyperlysinemia Peter's Anomaly

syndrome


Ectopia Lentis t congenital t

EL

J

t

Acquired t

Post Traumatic

Marfan's

Weil Marchasani Homocystinuria

Ehler Danlos syndrome Sticklersynd

Most common

oath

2

manifest

Retinal

Detach

Inferonasal EL micyspherophahia

Superoptemporeaf

Homotustinuria

Inmate.IT

pYanfmidsi'sIIIan

ui

eg


Homocystinuria

Inferonasal EL

Marfan's

Weitmarchasani Syndrome

BIL

Inferior EL

Superolemporal

EL t

Zonulav Disintegration

Intactanules

t

Microspherophab

40 Accomodation IntactAccomod 2 Matanoid features t

Thrombo

embolism

MentalRetard

Tall.thin Arachnodactyly

GothiclHighanhed palate

Tnt'Laxity

t pupillaryblouk glaucoma

Opposite K marfans

I

short fingers

shortstature


Stickler syndrome Hereditary Arthro

3main features High myopia Vitreous Retinal degeneration 4

RD

Cataract

Ophthalmopathy



3

3

waves L

1st

wave

waves

of NCC migration bln Lens

1

3rd

2nd wave

Endothelium of cornea Descend's memb

surface ectoderm

1

v

t

Ref

of NCC

t

t

Shoma of cornea

stoma of Iris pupillary

AAO 2019 woo

wave

membrane

some books say 2 l 3rd

wave

YnaeaYs mmas

in's


cornea

t

t

1

other layers

Epithelium t

t

from NCC

from surface Ectoderm

corneal Transparency 1

due to maturation of corneal Lamellae but failure of collagen

heratocytes

fibres

in

to

produce

Lamellar

t

Scleralisation of

cornea

Sotero cornea

Array


moderate Sdewcome a

severe Sdew

cornea

Differentials for Congenital Corneal Clouding

clew cornea Tears

in Des cemets

post Trauma

Iker M ucopolysaccharidosis Metabolic disorders

Peder's Anomaly

Posterior axialstromal defect

Edema CongenitalHereditary Dermoid

EndothelialDystrophy


Microcornea

us

Megalocornea

t

t Horizontal corneal diameter Elomm

in adults

Horizontal corneal

diameter 213mm in adults

f

Cor

9mm in newborn

Nole

corneal diameter 10mm 1

Neonates

12mm

Assoc Pigment

2 yrs till Adult

pension

Syndrome


I

s

a


Anterior Chamber

Posterior Chamber

pig

see

Primo

men

E ftp.eo.i.mesenchsylimteihbln developing in's Hens posterior

chamber

Pc

me


Trabecular Meshwork corneal endothelium

elopingcornea

Dgeveloping

Ncc Mesenchyme

e iieiine

t.fi Ac

CollectionFest

of

undifferentiated Ncc mesenchyme

t

Trabecular Anlage b

mu mean eY

Cinema

t

it

a


Trabecular 13Wh

Anlage

0

capillaries

y Trabecular

Ant chamber

to Pupillary

membrane

cells

Schlemm's canal Sc 22Wh

giant Vacuoles in SC

Enlarged Connective

Tissue

Inter Trabecular spaces

LTrabewfaveys


Schemm's Canal

me.sentiemme

Fm

from Ncc mesenchyme

Deep ATM collection of small capillaries fuse to form

single

elongated

slit likevessel

CANAL of Sc LE nm

from Mesodermaf Mesenchyme

vessel vacuoles

w

Endothelial cells


Trabecular Anlage

t

Trabeculen Meshwork Develops into x

3pqHs I

Innermost H Unreal Meshwork

l

Middle

H

Comeosderal Meshwork

I cord like

Lamellar

1

Outermost

Hi

Juxta canalicular

f Cribriform Zone f Loosely

arranged

Schlemm

Tuxtacanaticular Meshwork corneosderal Meshwork

fffcandoc

j 99

saved meshwork


Tn

Er Microscopic Anatomy of Tnt in Adults


GONIO DYSGENESIS Maldevelopment

of

Iridocorneal Angle

t

t

Trabeculedysgenesis

Fido

only

Isolated TM

corner

dysgenesis maldevelop

t

a

Impaired Aqueous outflow W o other major ocular abnormalities

I PRIMARY CONGENITAL GLAUCOMA

Mostimportantgene CYPIBI

1

Axenield Riegersyndrome

2

Peter'sAnomaly

3 Aniridia SECONDARY CONGENITAL

GLAUCOMA


Primary

Congenital Glaucoma

Triad

1 Epiphora

2 Photophobia

D Blephawspasm

I HAAB's STRIAE cut'rvilinear

healed breaks in Descend's membrane


Axenfeld Riegersyndrome to Axenfeld Anomaly

Riteger

Anomaly

f

4 Rieger syndrome

Reiger Anomaly Extraocular

1

prominenteanteriorly

manifestations

displaced

Schwalbe's line _posterior

f

Embryotoxon

peripheral

iris strands extending into cornea


Rieger's Anomaly mimics In do cornealEndothelial

ICE syndrome


Rieger's syndrome

Telecanthus

BroadNasalBridge MaxillaryHypoplasia

Dental Anomalies microdontia small teeth

Hypodontia

fewteeth

Peter's Anomaly

2

1

Corneal involvement

only Type

I

Corneatlens Type 2

Hallmark Central defect in Descemets's Endothelin Thinning opacified corresponding Shona


Central corneal opacity

Ii docorneal Adhesions

Lenticulo corneal Adhesions


Eye Lids

fusion of Lids complete

GA

10wks of


mesoderm

yureof 1

Tarsal

plate

lqwksremainfusedtill28thwhlSacendosedbyfusedlidsft.y

Conjunct sac

Corneal Epithelium

lined

I

by ectoderm


r

cornea

Note

failure of I

Lidformation

t

t c

Lidfusion

Lidseparation

CotoBomA

CRYPTOPHTHALMOS

Assoc

T

Fraser

Syndrome

Away BLEPHARON

I


LID

COLOBOMAS

2 syndromes Treacher Collins H

Lower Lid coloboma details given later

Goldenhar H Upper lid coloboma

1

Triad

Peribulbar dermoid Pre auricularappendages Pre tragal fistulas


Goldenhav syndrome

limbaldermoid

Preauriculattags


Epicanthus in versus

foldof skin extending from lower lid to medial 1

canthus

1

Assoc I

BPES

Blepharophimosis

Ptosis Epicanthus inversus syndrome


Telecanthus f

Bendohyperklorism

Abnormally ton

medial

canthallIndons

I fed distance bln medialcanthi

f

TInnercanthal distance

OCD

IPD

us

Hypertelorism 4

wide bonyseparation of orbits

f

orbital Hyperklorism I

manifestation of

a

craniofacial deformity TICD OCD IPD OCD Outer Canthal Distance

IPD Inter

pupil Dist

ICD Inner

canthd pistons


edetainthus Hyterlelorism


Orbit

contents

Striated ExtraocularMuscles

Bones Tendons Intermusadarseplae ConnectiveTissue AdiposeTissue

Neural CrestCells

Note All bones

are membranous except

cartilaginous

sphenoid

3rdmonth

Ossification

2

of GA

f 7thmonth

7

fusion

Mesoderm


Congenital Craniofacial Abnormalities

f

t Non synostosis

craniosynostosis

t

t

Branchial ArchSyndrome 4

Premature fusion of

Cranialsutures

failure

of Development of 151 2 Branchial Arches

f

I

3 syndromes L

2 syndromes

I

Aperisterouson Pfeiffer

Treacher

Goldenhar

coins

t Mandibulofacial Dysostosis

i

nYdD


Apeitsyndrome most

severe

craniosynostosis

mid facial Hypoplasia

Parrotbeaknose

syndactyl

oxycephaly

CConicalskull Lowsetears


Gougon Syndrome Midfacial Hypoplasia shallow orbits

Proptosis

Hypertelorism

Shot anlocoposterior Diameter of Shul


Pfeiffer syndrome a

cloverleaf shaped

skull

1

Exorbilism spontaneous profusion of eyes

due to shallow orbit


Treacher Collins Synd Downward slantingeyes

Bk

Hypoplasia

of mandible

Zygoma

Lower

Lid

colobomas

Punctal Atresia


Lacrimal Gland NasoLacrimal Drainage

surface Ectoderm

LacrimalGland go.sepittdialbudsfwmfoyyngngn.nl

Nonfunctioning till

bwnsglik

Newborn don't tearup when

they cry

Congenital ALacrimia ltypoplastiahbsI.tljyeeye.inyoung


Lacrimal Drainage

Vaso lacrimal Groove

blnfwntonasal Maxillary process

Isolated cavities

solidepithelial cord

5 swhsot GA

complete

canalisation

4h7 9thmon


NasoLacrimal Duct patency

1

completes

monthof 7th by life

H Incomplete canalisation of NLD

1 Congenital

NLD obstruction

th MC

c

Imperforate Hasner's Membrane

Value of Hasner lowerendof Last part to canalised

NLD


Epiphora in Newborn

t Congenital Is

L

l

Acquired

EffITgenimeDaoyogstowe NLD

Punto

IngenitalNLDObslmoti

H

Agenesis

Atresia

Fistula

t

Eanalicular Agenesis

Atresia

Most common cause of Epiphora in

Newborn H


Non Patent NLD

Competent Valve

of Hasner

Collection of Amnioticfluid Mucus in Lacrimal sac

Amniontocede Congenital Dacryocele

perinatal bluish cystic swelling

or

below medial canthus

DD

Encephalocele

k

above medial canthat

tendon


GENETICS Master Gene in

developmentof Eye

PAX 6 gene mutation

PAX G

Paised Box 6gene

t

Coloboma Microphthalmia Peters

t

Anomaly

Generesponsible for Division of Eyefield into 2 eye Globes SHH Soni'T Hedgehog


PAX6 expression

PAX

G

switch

for eye development


D

D


Holo Prose N CEPHALY

Defect in SHH

Gene

Proboscis

Cyclopean

fSyn

Eye

ophthalmia7

ANOPHTHALMIA failure offormation of opticVesicle to

attain e

any

visible globe structure


MICROPHTHALMIA to Complex

simple_Pure

f

Nanophtralmos

t

Structurally

Associated features

eyeball

of Dysgenesis

short Axial length

oboma eg.co orbital cyst Bllolobomas

Orbital

cyst


COLO BOMA

Mutilation

PAX 6 gene mutation

Chtoidal

1

fissure hot closed Normally closes by 7th week

Coloboma

Isis ciliary

Body 2onules

H

t

Retinae choroid Recoloboma

optic Disc x

µ

ODpit

Axial Coloboma of OD

MORNING Glory

SYNDROME

M.c.sie Inkronasalheyhole defect of iris Typical

Coloboma


Calamitous lens

Hq

keyholedefectinin's

I

ymissingzonules

2ondaddoboma

Types I

Typical

It

Inferonasal quadrant closure fissure choroidal site

of

Atypical other areas macular'Toloboma

is also atypical Atrial

Complete

fulllhickness

defect

E Incomplete

Partial thickness defect of epithelium stroma


Retinochoroidal Globo ma

r Retinalvessels down

dip

Excavated area Exposing

yo RPE

bare sclera

Edges dean cut

Choroid


Histopathology Inner Nyagkey ppenfierarm

SplitinNeurosensory Retina

Layer

a

ignerlayer

Intercalary membrane

7 t.TT

sFsRPElchaoid

outer layer fusey.si RPE

Termination

Disorganised mass

of choroid

H Junction Locus Minoris Resistentiae


Pathophysiology fetal fissure closure

Defective

t

Inner Layer of opticCup growsfaster than outerLayer future RP E

f

Eversion 11

Gradual displacement of RPE t

Double Layer of photoreceptors

facing

each other

Absent RPE

1

Absent choroid


Ida Mann

Classification

AboveDisc

superior bogda

Below disc

Nimue area of

bn

Retina OD Globo ma


Isolationism

J so

pigmendfoftwbana

extreme


Classification of RC Globoma Gopal Lingam 19967

NO Disc

I

OD is outside fundus coloboma

Abnormal Disco

I

I I

Colobomalous Disc

isolated

Disc

OD is within Fundus coloboma

I

ColobomatousDisc 4

I

Disc shape not identified Blood vessels emanating from superior aspectof large fundalwlobom


Classification Gopal Lingam

I

I

o

E

x f

I

r

f

I

abnormal

TI

I

I

r

TI

III

I

I

Visual Acuity Good myopia High

Microphthalmos

common


OD Colo boma focalglistening while bowel shaped excavation

Inferior NRR

1

Absent

Thin

Assoc O D pit


Association

of

Hoboma

Rhegmatogenous

RD

CHARGE syndrome

I

401

CHD7 geneinvolved

Edoboma HeartDefects

Atresia choanae Retarded growth

Genital hypoplasia

Ear malformation

AICARDI syndrome WARBURG syndrome


Note

Lens Coloboma

Misnomer CB

coloboma

I Absence

ofwhales

1

Indented Lens


BIG PICTURE

orbit

Efm

NYids

migrating

Sark

Ectoderm

sypienophab

1

i

II

NTeuralabe

ftp 7Iweloph.g

mean Lens Hyaloidvessels

Neuroectoderm

Future Retina

Neuroectoderm

Neural crest Mesenchyme surface Ectoderm mesodermal Mesenchyme


SUMMARY

Go throughagain



the derivatives been of Summary Repeated to have the

the of understanding

final

Big

Picture


References


For relevant video based discussions on embryology and more topics Visit YouTube.com/kingsclasses



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