Neuro-embryology

Unit 3

Week 1- Formation of the Blastocyst

• Day 1: Fertilization

• Day 2: Two Cell stage

• Day4: Morula

• Day 5: Early Blastocyst

trophoblast

Outer layer of blastocyst thins to one cell layer thickness

embryoblast

the inner cell mass of blastocyst differentiates

Week 2 - “Week of Two’s”

* Implantation
* Embryoblast (Inner cell mass) differentiates into two layers :
* Epiblast
* Hypoblast
* These two layers form the bilaminar embryonic disc
* The trophoblast differentiates into two layers:
* Syncytiotrophoblast
* Cytotrophoblast

Describe the blastocyst on day 5 and on day 6

day 5: organizing, early

day 6: well organized, implanting

what stage is the embryo in on day 4?

morula

What part of the trophoblast implants?

Synctiotrophoblast

What part of the trophoblast is close to the bilaminar disc

Cytotrophoblast

Embryonic stem cells

totipotent, pluripotent

Adult stem cells

multipotent, oligopotent

Totipotent

Can create any cells of the body and placental cells, represents the first fertilized cell and first few divisions, can develop into any mature cell type

Pluripotent

Derived from totipotent stem cells cand form any of the 3 germ cell layers, can develop into any mature cell type

Multipotent

These stem cells can develop into a group of related cells, are also contained in the amniotic fluid

Oligopotent

Very limited cells, can differentiate into specific cells only, example myeloid or lymphoid cells

Unipotent

Can produce only their own type of cell, and can self-renew

Induced Pluripotent

These are adult cells that are reprogrammed by genetic protein transcription to become pluripotent

What 2 cavities form in week 2

amniotic cavity and yolk sac

When does the amniotic disc form?

week 2

Day 9

lacunae or clefts appear

Day 12

extra-embryonic coelom and chorionic cavity starts to appear

Day 14

* primitive utero-placental circulation begins
* blastocyst is fully embedded, and mucosa has healed
* **primitive streak** appears on the epiblast
* epiblast shows an orientation (up, left/right)

What factors are secreted to inhibit the nodal activity in the cranial end of the embryo

* cerebus
* LEFTY

What establishes Left/Right in an embryo? How?

Sonic hedgehog ligand by stimulating Nodal and LEFTY

What side is LEFTY expressed on?

Left lol

What side is activism expressed on?

Right

Why is Sonic hedgehog ligand important during **week 5-6**?

it is responsible for formation and patterning of the neural tube

* creates separation of lobe and face
* creates two eyes

What are the degrees of severity for holoprosencephaly?

1. lobar
2. semilobar
3. alobar

Gastrulation

epiblast forms the 3 germ layers: ectoderm, mesoderm, endoderm

When does gastrulation occur?

week 3

Describe the gastrulation process

1. epiblast invaginates to form the endo- and mesoderm
2. ectoderm forms the neural plate and becomes neuroectoderm
3. invaginating cells reach the prechordal plate and form the notochordal plate

When does neurulation occur?

Day 18-24

Neurulation

process by which the neural plate forms the neural tube

What initiates neurulation?

non-migrating neuroectoderm

Describe day 18

* neuroectoderm induces neurulation
* midline mesenchyme releases chemical signals to ectoderm and forms neural plate
* notochord detaches and forms solid cord

What is the neural plate notochord derived from

epiblast cells that invaginate and become part of the hypoblast

describe day 20

* folds form around the neural streak
* form a neural groove
* lateral folds of the neural plate elevate to form the **neural folds**
* top of the cells on the neural folds develop the **neural crest cells**

describe Day 22

* parasail mesoderm forms the somites
* the cranial and caudal neuropores remain open
* neural tube starts to close

describe Day 24

* neural fold cells leave behind the neural crest cells
* neural crest cells develop the dorsal root ganglia
* rostral end of neural tube closes

Day 26

caudal end of the neural tube closes

Somites become _

spinal vertebrae

Neural tube becomes _

CNS

Neural crest becomes _

PNS

Neural crest develops to form _

neuroectoderm

What can failure of migration of neural crest cells cause in the PNS?

* congenital deafness
* cardiac abnormalities
* autonomic abnormalities
* pigmentary abnormalities

Albinism

pigmentary abnormality where there is a block of tyrosine by tyronsinase into melanin

Type of albinism when there is failure of migration for **neuroectoderm**

* ocular albinism due to low number of mature ocular melanosomes
* iris and RPE affected, macular hypoplasia and nystagmus

Type of albinism when there is failure of migration for **neural crest**

albinoidism - skin, hair, iris stroma

Type of albinism when there is failure of migration for **neuroectoderm and neural crest**

oculocutaneous albinism due to inadequate melanization of a normal number of melanocytes

Facial abnormality that can occur due to failed neural crest migration

* neurocristopathies
* treacher-collins-franschetti syndrome
* cleft lip and cleft palate

What does fetal alcohol syndrome impair?

neural crest migration

General effects of FAS

* mental disabilities
* progression of symptoms

Ocular effects of FAS

* causes reduction of retinal cells
* microphthalmia (small eye)
* optic nerve hypoplasia (small ON)

In the neural tube, what is the ant. and post. neuropore in contact with?

amniotic fluid

What does the neural tube become?

* ventricular system of the brain
* central spinal canal

What does the outmost layer of the spinal cord become?

marginal layer → white matter of spinal cord

gray matter of dorsal half forms

alar plate

gray matter of ventral half forms

basal plate

Sulcus limitans

separated the neural tube into ventral and dorsal halves

Notochord cells

make Sonic hedgehog and induces the floor plate to also make SH

Longitudinal groove

occurs in the lateral wall of neural tube

How old is the embryo when it has 8 somites

22 days

How old is the embryo when it has 10 somites

23 days

Somitomeres turn into..?

somites

What do somites turn into?

axial skeleton (skull and spine, hence spinal vertebrae)

How many somites can an embryo have when it is 20-21 days

1-4

How many somites can an embryo have when it is 28-30 days

30-35

What does the intermediate mesoderm become?

urogenital system

What does the intermediate mesoderm line?

* wall of gut
* peritoneal, pleural, and pericardial cavities and secrete serous fluid

When does secondary neurulation occur

Week 5-6

How does the sacral spinal chord form?

secondary neurulation

Describe the process of secondary neurulation

* caudal cell mass consisting of mesenchyme cells form medullary cord
* form vacuoles that coalesce to form a central canal
* neural tube and sacral tube join

Rostral neural tube defective closure

anencephaly

How can neural tube defects be detected in maternal circulation?

alpha-fetoprotein

What supplements can mothers take to prevent neural tube defects?

Folic acid

Open neural tube defects

* entire CNS affected
* anencephaly
* hydrocephalus
* Chiari II malformation

Closed neural tube defects

* spine only affected
* spina bifida
* no exposed neural tissue
* skin of defect may be dysplastic

Spina bifida occulta

malformation of one or more of the vertebrae of the spine (usually no problems)

Meningocele

meninges protrude through a gap in the spine

Myelomeningocele

meninges and spinal cord develops in a fluid-filled sac outside of the body

What is a Chiari Type 2 Malformation

cerebellum and caudal brainstem are pushed down into foramen magnum

Week 4/Day 28

* post. neuropore closes
* neurulation complete
* closed spinal cord
* development of sulcus limitans and sonic hedgehog

What placodes can be seen at week 4?

* otic placodes
* olfactory placodes
* medial & lateral
* optic placodes
* profundal/trigeminal placodes

Structures from Telencephalon

* ==cerebral hemispheres==
* ==lateral ventricles==
* ==intraventricular foramina of monro==
* ~~hippocampus~~
* ~~basal ganglia~~
* ~~amygdala~~
* ~~cerebrum~~

Structures from Diencephalon

* ==optic cup and stalk==
* ==pituitary==
* ==epiphysis==
* ~~thalamus~~
* ~~hypothalamus~~

Structures from Mesencephalon

* oculomotor and trochlear motor nuclei
* EW nucleus
* Crus Cerebri
* Superior and inferior colliculus

Structures from Myelencephalon

Medulla oblongata

Structures from Metencephalon

* ~~Pons~~
* ~~Cerebellum~~
* Pontine Nuclei
* Rhombic lips

What do the rhombic lips form?

cerebellum

What is the cerebellum responsible for?

coordination center for posture and movement

What is the pons responsible for?

pathway for nerve fibers from the spinal cord to cerebellum and cerebrum

What are the type of motor neurons that arise from the basal plate of the metencephalon

* somatic efferent
* special visceral efferent
* general visceral efferent

Somatic Efferent motor neuron

gives rise to the nuclei of the abducens nerve

SVE motor neuron

contains the nuclei of the trigeminal and facial nerves

GVE motor neurons

axons supply the sub-mandibular and sublingual glands

What is the phylogenically oldest lobe of the cerebellum?

flocculus

Noduloflocular lobe responsible for..?

eye movements