05 Gastrulation Neurulation Heart Complete

7/30/2019 05 Gastrulation Neurulation Heart Complete

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Gastrulation - Cell Lineages


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Blastocyst

Embryo pole

Inner cell mass(embryoblast)

Blastocoel

Outer cell mass

(trophoblast)

abembryonic pole


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Day 6

Blastocyst adheres to

endometrium at embryopole

Trophoblast proliferation

production of hCG(maintains corpus luteum)

Epiblast Germ Layers

Inner Cell MassExtraembryonic

Endoderm/MesodermHypoblast


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Bilaminar DiskEpiblast and Hypoblast

DelaminationSeparation of the Inner Cell Mass


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Amnion

Amnion forms from epiblast

CavitationFormation of an internalspace within a tissue

From BM Carlson, 1999


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Gastrulation

EpiblastPrimary Germ Layers

Ectodermouter layerSkin, Nervous

System, etc.

Mesodermmiddle layerMuscle, Bones, etc.

EndodermInner layerDigestive Tract, Lungs, etc

ProcessMorphogenetic MovementsOrganized Cell Migration


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Primitive Streak


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Primitive Streak

Embryonic Day 15Primitive grooveinitiates gastrulation

Primitive Streakincludes groove, node

The Primitive Streak defines

Anteriorcranial PosteriorcaudalRight and Leftlateral

and pit

Streak extends cranially then regresses caudally

the notochordal process during regression.

depositing

The tip of the regressing streak is the Primitive Pit and the

Primitive Node (also called Hensens Node)


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Primitive Node/Pit


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Bottle Cells


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Endoderm

First cells to go through the Streak form the EndodermalThese cells integrate and displace hypoblast cells


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Mesoderm

Complex pattern of movements

Streak formationLateral MigrationCardiac

mesoderm

Streak regression - Lateral and Cranial Migration

Lateral Plate Mesoderm Somitic Mesoderm

Streak RegressionCentral and Cranial MigrationNotochordcellular rod, central long axis of embryo


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Mesoderm


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Ectoderm

Ectodermal cells dont enter the streak

Cell layer expands as endodermal andmesodermal cells enter the streak

Cranial to the notochordectoderm andendoderm are in direct contact

Oropharyngeal membrane

Between the Oropharyngeal membrane andthe notochord is the pre-chordal plate

important for inducing the brain


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Notochordal Process


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Notochord


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Embryonic Induction

Definition: Signal from one group of cells

influences the development

adjacent group of cells

Inducing Tissue or Inducer

Inductive Signal - Morphogen

Responding Tissue Competence

Expression of Target Gene

of an


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Primary

Induction


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Embryonic Induction

Definition: Signal from one group of cells

influences the development

adjacent group of cells

Inducing Tissue or Inducer

Inductive SignalDe-Repressor

Responding Tissue - RepressedCompetence

Expression of Target Gene

of an


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NodalRequired for primitive

streak formation

Lim1 Homeobox containing;

Node and pre-chordal plate Null

- Headless

HNF3Hepatic nuclear factor;Notochord formation

BMP4 Bone Morphogenetic

Protein4; represses dorsal

ectoderm

Noggin and ChordinBMP4

inhibitors; de-represses ectoderm

neural tissue


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Lim1 Mutant


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Left-Right Asymmetry

Node Signals:

SHHSonic HedgehogLeftinduces Nodal

ActivinRight (inhibits SHH)

Reverse Asymmetry = situs inversus


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Notochord as

Inducer

Induces overlying ectodermNeural(Neural Induction)

Tissue

Specifies cell type in the Floor Plate of theNeural Tube

Transforms para-axial mesoderm (somite) into

vertebral bodies

Stimulated early development of the dorsalpancreas


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Neural Plate


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Mesoderm


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Paraaxial Mesoderm - Somites

plate


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plate

Somite

Notochord

Henson's node

Primitivestreak

S it i


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Somitogenesis

d18-d28Cranial to Caudal37 somitesform muscle, dermis,skeleton

Somitomeres 1-7 do not form somitesmigrate to Pharyngeal

Arches, muscles of face, jaw, throat

Somitomere 8 forms Somite; rate of 3-4 somites / daySomite

Somite

Somite

Somite

Somite

Somite

1-4Occipital Region (skull, nose; ocular m., tongue

5-12Cervical Region (Cervical vertebrae, neck dermis)

13-24

25-29

30-34

35-37

Thoracic Region (vertebrae, arms)

Lumbar Region (abdomen, legs)

Sacral Region (sacrum) Coccygeal

Region (coccyx)


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Segmentation of the Embryo

Segmentation occurs along the Anterior-

Posterior Axis

Each segment becomes an autonomous

developing unit

Each segment can grow and undergo furthersegmentation

Molecular mechanisms are conserved

Maternal ePect genes E t bli h di t M j di t bB!co!d


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Maternal ePect genes Establish gradients

from anterior and

posterior poles of

the egg

Major disturbances

in anteroposterior

organization

B!co!d

Swallow

Oskar

Caudal

Torso

Trunk

Segmentation genes Define broad

regionsin the egg

Empty spiracles

HunchbackKrdppel Knirps

Tailless

Adjacent segments

missing in a majorregion of the body

Gap genes

Define 7

segments

Pair-rule genes Hairy

Even skipped

Runt

Fushi tarazuOdd paired

Odd skipped

Paired

Part of pattern

deleted in every

other segment

Segment polarity genes Define J 4

segments

Engrailed

Gooseberry

Hedgehog

Patched

Wingless

Segments replaced

by their mirror

images

Homeotic genes Antennapedia

complex

Bithorax complex

Determi ne regional

characteristics

1 nappropriate

structures form

for a given

segmental level


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Drosophila

, AT.C BX'C

J0 JJ

J2

J3

Hoxe (Hox-J)

Fluman

ue1F

I.aJ K

i.i iJ 1 D J C

i.sJ R

i.z]

,4,

i.I

JG

J ,

2

IH

J

AB

J I

J .9is

ic

I J0

6

Hoxb (Hox-2)

Hoxc (Hox-3)

Direction of trznscri ption of FJoxgcris


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d f


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Hox Genes Encode forTranscription

Factors


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Gastrulation

Caudal Dysgenesis (Sirenomelia)

Caudal defect

Insufficient mesoderm formation

Anomalies

Fused lower limbs, renal

Genetic and Teratogenic

Brachyury (T), Wnt

agenesis

Holoprosencephaly

Cranial defectNeuronal and craniofacial cell death

Small forebrain, fused ventricles

Teratogenic, e.g. alcohol


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Neurulation

Readings:

Chapter 5

Chapter 10P.

P.

p.

208-214

218-219

239-240

(Peripheral Nerve)

(Cranial Nerve)


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Neurulation

Induced by NotochordNoggin/Chordin

Neural PlateNeural GrooveNeuralTube

RegionalizationSubdivisions of the CentralNervous System (CNS)

Noggin, chordinAnterior Neural

Forebrain

Tissues

FGF8Fibroblast Growth Factor 8Posterior

neural tissues, i.e. spinal cord


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Middle of third week:

Neural Plate

Notochord induces

overlying ectoderm

neural plate

Thickening of cell layer

Anterior Inducer:Noggin/ Chordin

Posterior Inducer:

FGF-8,


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Neural PlateNeural Tube

Four Stages of Neural Tube formation:

1)

2)

Thickening of the Neural Plate

Establishing the contours of the NeuralPlate: Cell shape changes and

rearrangement of cells

Lateral Neural Folds elevate to form the

Neural Groovemedial hinge acts as ananchor, Cell shape changes apically,

expanding lateral epidermis forces

elevation

3)

4)


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Coelom icspace

Paraxial

mesoderm

Lateral

mesoderm

tteeeeteeeee

tteeeeeteeete

Neural

Lateral

foldSomiteI ntraembryoniccoelom

crest

Neu ral tube

Somatic mesoderm

Splanc hn ic

mesodermNotochord


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Neural

Crest


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Early CNS

Development


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Neural Tube Formation

Anterior Neuropore

Anterior

Central Fusion CompletionClosure of Neuropores

Posterior

Posterior Neuropore

Secondary NeurulationPosterior to the neuropore

Mesenchymal condensation to form a rod that undergoes

cavitationsecondary fusion with primary neural tube.


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Segmentation of the Neural Tube


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Tele

Ep

Di

ee'

teMese

reb

cereb

ho


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Segmentationof

theRhombencephalon

NeuromeresTransient regularly spaced

also called Rhombomeres

7 pairseach an isolated compartment

segments,

Alternating cell adhesive characteristics;

rhombomeres intermingle freely

alternating

Segmental organization gives rise to specific cranial

nerves


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Specification

and

Position-

SpecificGene

Expression


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Tele

Ep

Di

ee'

teMese

reb

cereb

ho


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Cephalic flexure, Cervical flexure, Pontine flexure


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Cerebrum

Thalamus CorpusCallosum

Pineal BodyHypothalamus

Midbrain Cerebellum

Pons

Medulla

oblongata

Hi t i f CNS ll


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Histogenesis of CNS cells

C ll T


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Cell Types

NeuroepitheliumMultipotentialBipotential Progenitor Cell

Neuronal vs. Glial Cell Lineage

Neuronal Lineage (neurofilament

Stem Cell

expression):Bipolar neuroblast, Multipolar neuroblast,

Neuron

Glial Lineage (glia fibrillary acidic protein, GFAP):

Radial glia, Type-1 Astrocyte, Type-2

Astrocyte, Oligodendrocyte

Mitosis

ceases


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Bipolar

neuroblast

Multipolar

neuroblastMature neuron

Neuronal

lineage

progenitor

cell

Mesenchy

cehN4Ros!

sceases

V!ccogha

!cell

Oligodendrocyte

progenitor cell Oligodendrocyte

Mitosis

ceasesFew mitotic

sions

Mitosis

0-2A

progenitor cell

Mitosis Mitosis

Type-2 astrocyte

progenitor cell

Transitional

stage

Type-2

astrocyteNumerous

mitotic

ivisions

Bipotential

progenitor cellMitosis ceases

t .. t ..Type-J

astrocyteGlial lineage Type-J astrocyte Transitional

Special glialogenitorcell

Multipotenti

aistem cell

'' cells (e.g.,

Bergmann cell

Mitosis ceases during MUttercells)Mitosis

Radial

progenitor cell

Radial

glial cellMorphological

transformation of

radial glial cells

Neuroepithelium Ependymal

cells


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Dendrite

Cell Body

Axon

Schwann Cell

Myelin Sheath

DendriteDendrite


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Cell body

Cell body

/v\yeIinoted oxonMyelinoted oxon

To centrol

system

To centrol nervous

sysfem

Cell body

Myelinoted oxon

Dendrites

Oligodendroglial cell


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Unmyelinated

axon

Schwan n

cell cytoplasm

Node of Ranvier

Myelin

leaflets

Schwann Cell nucleus

Axon


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Spinal Cord

Central CanalLumen

Ventricular ZoneCells

lining the Central Canalbecomes Gray matter

Intermediate Zone Marginal

Zoneneuronal

cell processes; no cell

bodies, becomes White

matter


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6 Parts of the SpinalCord

2 Alar Plates (Left and Right) Sulcus

Limitans separates Alar

and Basal plates

2 Basal Plates (Left and Right) Roof

Plate connecting Alar plates FloorPlate connecting Basal plates Basal

platesMotorVentral Horn Alar

platesSensoryDorsal Horn


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Nerves

Motor

Sensory

Autonomic

Sympathetic

Parasympathetic

ganglion IX ganglion VII Trochlear nerve IV


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OculomotorSemilunar

ganglion V

nerve 111Inferior

ganglion IX ganglion VJI }

Superior

ganglion XRoots ofvagusnerve X

Commissural

ganglion

Spinal accessory

nerve XI

Hypoglossal

nerve XP 1

First cervical

ganglion

Opthalamicon, nerve V

Inferior

ganglion X

Facial nerve

Mandibular

ivision, nerve VAbducen

s

nerve VILingual nerve Chorda

tympani nerve division, nerve V

Cranial Nerves


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Cranial Nerves

I. Olfactory; Telencephalon; No Ganglion;Sensory

II.

Optic; Diencephalon; No Ganglion; Sensory

III. Oculomoter; Mesencephalon; Cilary

Ganglion; Motor and Parasympathetic

IV. Troclear; Metencephalon; No Ganglion;

Motor VTrigeminal (semilunar);

Metence halon,


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VI. Abducens; Metencephalon; No Ganglion;

Motor

VII. Facial; Metencephalon; 4 GangliaSuperior,

Inferior (Geniculate), Sphenopalatine,Submandibular; Motor, Sensory,

ParasympatheticVIIIVestibulocochlear; Metencephalon, 2

Acoustic, Vestibular; Sensory

Ganglia


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IX.Glossopharnygeal; Myelencephalon; 3 Ganglia

Superior, Inferior (Petrosal), Otic; Motor, Sensory,Parasympathetic

X. Vagus; Myelencephalon; 3 Ganglia Superior,

Inferior (Nodose), Vagal parasympathetic; Motor,

Sensory, Parasympathetic

XI.Accessory; Myelencephalon; No Ganglia; Motor

XIIHypoglossal; Myelencephalon; No Ganglia;

Motor

MidbrainMidbrainForebrain Dtence halon HindbrainHindbrain


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Auditor

yvesicle

VII and VI1 1

Auditory pit

Arch 1

Arch 11 Opticvesicle

Heart

Telencephalon

VII and VIII

halon

HindbrainMidbrainMesence Metencephalon

MyelencepDiencephalon

Spinalcord

Telencephalic

vesicle Spinal

cordTelencephalic

vesicle


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Cerebral

hemisphere

(telencephalic

vesicle)

Diencephalic outline

Superior colliculus

Inferior colliculus

Mesencephalic

Cerebellum (metencephalon)

Olfactory lobeMedulla (myelencephalon)

Chord a tyre paniOphthalmic branch (V)

Maxillary branch (V)

Mandibular branch (V)Spi nal cord

Larynx


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Anomalies

Defective Neural Tube Closure

Spinal CordRachischisis Brain

Craniochisis (lethal)

Spina BifidaDefective closure of anterior orposterior neuropore

lacking neural arch, bulging membranous sac called a

containing cerebral spinal fluid +/- neural tissues

Spina bifida occultaDefect in Neural Archmildest form

Meningoceleprotruding dura and arachnoid tissues

Meningomyeloceleprotruding spinal tissues

Meningoencephaloceleprotruding brain tissues

Cele,

Meningohydroencephaloceleprotruding brain and ventricular

tissues

Anomalies Spinal Cord


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Anomalies Spinal Cord

Rachischisis Spina bifida occulta

Meningocele Myelomeningocele

Spinal Abnormalities


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Spinal Abnormalities

Spina bifida

Brain Abnormalities


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Brain Abnormalities

microcephaly

holoprosencephaly

hydrocephaly

Early Heart Development


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Early Heart Development

Precardiac mesodermhorseshoe shaped extendingon both sides of the foregut

Endoderm induces early heart tissue

back

Mesoderm splitssomatic and splanchnic, cardiogenicplate is splanchnic and anterior to the oropharyngealmembrane

Space between somatic and splanchnic mesoderm will formpericardial cavity

180o rotation of the anterior embryo places the heartosterior to the oro har n eal membrane

Neural plate


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Oropharyngeal membrane

Cardiogenic

enic mesoderm

plate

Cardio

Foregut

Oropharyngeal

membrane

Heart tube

Pericardial cavity

H t F ti


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Heart Formation

Vesicles in the pre-cardiac splanchnic mesoderm

fuse to form paired endocardial primordia on bothsides of the foregut

Endocardial primordia fuse along the midline toform the primitive tubular heart

Inner endocardial lining becomes the endocardium,surrounded by matrix called cardiac jelly

Myocardium surrounds the cardiac jelly

Myoca diarimordiu

P i di l

Dorsal ao


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t

7

Pericardial

coelom

Cardiac

]elly

-somite embryo

'20 days)

4-somite embryo

('2 ays

Neural tube

DoNeu I groov

at aorta

NAyoc

ar

7-somite embryo

('22 days)

J0-somite embryo

('22+ days)

' Neural tube

Foregut


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Endocardium

Myocsrdisl

Ventral aorta

Fusedcndoczrdial

tubes

Omphalomcscntcric

Heart Formation


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Heart Formation

Tubular heart forms an S-shaped loop


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Aortic roots Primitive IimitiveI a ri

Pericardi miti


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alcavity

righ

Bulbuscordis

,

Pericardiume

TrabI ri

culated parventricle

Le ven ricle Int ent icula sulc


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Blood and Vessels

Blood forms from blood islands in the Yolk Sac

Extraembryonic splanchnic

Induced by extraembryonic

Stem cell = hemangioblasts

mesoderm

endoderm

in the bloodislands

Blood-forming cells = hemocytoblasts

Vessel forming cells = endothelial cells

in primordial Splanchnic mesodermblood island of yolk sae


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Yolk sae

endoderm

EndotheliumBloodislands

Blood cells

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05 Gastrulation Neurulation Heart Complete