44. Brain Development

Question 1

Gastrulation - what happens and when?

Answer 1

Day 16
Primitive streak initiations formation of 3 germ layers (ectoderm, mesoderm, endoderm)
Paraxial mesoderm forms
Neural plate forms at cranial end first
Notocordal plate gives rise to notochord (mesoderm derivative)

Question 2

Neurulation - what happens and when?

Answer 2

Formation of neural tube from ectoderm - regulated by notochord signals
Primary neurulation: formation of neural folds (cranial closure D24, caudal closure D26)
Secondary Neurulation: closer of SC distal to S2 and filum terminale - begins on D27

Question 3

Which plates of the spinal cord give rise to sensory neurons vs motor neurons?
What molecules organize these neurons?

Answer 3

Alar (dorsal) plate = sensory neurons
Basal plate = motor neurons

Shh: higher conc ventrally = organizes motor neurons
Wnt/Bmp: higher conc dorsally = organizes sensory neurons

Question 4

What are the embryonic dilations and when do they occur?

Answer 4

W4: Forebrain (Prosencephalon), Midbrain (Mesencephalon), Hindbrain (Rhombencephalon)

W5: Forebrain (Telencephalon, Diencephalon), Midbrain (Mesencephalon), Hindbrain (Metencephalon, Myelencephalon)

Question 5

What are the adult wall, cavity, and CN of the final W5 embryonic dilations?

Answer 5

Telencephalon - cerebral hemispheres, lateral ventricles, CN1
Diencephalon - thalamus, third ventricle, CN2
Mesencephalon - midbrain, cerebral aqueduct, CN3
Metencephalon - pons, cerebellum, upper 4th ventricle, CN4*,5,6,7,8
Myelencephalon - medulla, lower 4th ventricle, CN9,10,11,12

Question 6

What is the most common CNS anomaly?

Answer 6

Neural Tube Defects

Question 7

Anencephaly

When it occurs, risks, biomarker, what happens

Answer 7

No brain development (lethal)
During W2-3
risks: maternal hyperthermia, vitamin deficiencies (folate, Cu, Zn)
marker: elevated alpha-fetoprotein

Question 8

Myelomeningocele

what it is, clinical features

Answer 8

Most common SC abnormality in development
Compatible with life
Meninges herniation from SC
clinical features depend on spinal level involved

Question 9

Holoprosencephaly

What it is, classification, assoc

Answer 9

defect in ventral induction - vesicle development/separation
most common developmental disorder of human forebrain
no signal to indicate cleavage of cerebral hemispheres
Class by degree of separation alobar vs. lobar
Assoc: Trisomy 13, Shh mutations (role in pattern differentiation)

Question 10

Neuroepithelial Cell Proliferation

What occurs, Time frame, signaling molecule

Answer 10

W3-5: symmetric proliferation of radial glial cells (scaffold for other cells)
W5+: asymmetric cell division (differentiation)
W7: development of cortical plate
W18: 6 identifiable layers
W24: gyral formation

High Shh: more neuronal proliferation
Low Shh: more neuronal differentiation

Question 11

Microcephaly

what it is, features, causes

Answer 11

Disorder of neuronal proliferation - small head circumference
Underdeveloped cerebral hemispheres, decreased normal skull dimensions
Due to multiple gene defects and complex causes

Question 12

Corpus Callosum Development

what occurs, time frame

Answer 12

W8-19 thru 18years
1st neurons = cingulate cortex - path for neocortical areas
Glia required for callosal formation

Question 13

Agenesis of Corpus Callosum

what it is

Answer 13

defect of cell proliferation, migration, axonal growth, glial patterning resulting in no corpus callosum

Question 14

Neuronal Migration
(How are excitatory and inhibitory neurons generated? Where do oligodendrocytes and astrocytes migrate from?)

Answer 14

Excitatory: generated by Pax6-radial glial cell in dorsal telencephalon (radial migration)
Inhibitory: generated by Nkx2.1 and Gsx2-radial glial cell (tangential migration)
Oligodendrocytes: from dorsal and ventral parts
Astrocytes: from dorsal parts

Question 15

Lissencephaly
(what is wrong?)

Heterotopias
(What is wrong, CP, types)

Answer 15

L: disorder of migration, abnormally smooth cortex (genetic causes)

H: disorder of migration, groups of neurons do not migrate well (CP: seizures/cognitive delay)
Types: subcortical, periventricular, leptomeningeal

Question 16

How is the cortex organized?

What is Polymicrogyria? CP?

Answer 16

Inside-Out Proliferation (outer layer 1 = newer)

PMG: disorder of organization = increased gyration, CP: seizures, cognitive delay

Question 17

Gliogenesis vs. Synaptogenesis
(mLc expressed, time, what occurs)

What is MECP-2 Related Disorder (Rett Syndrome)?

Answer 17

Gliogenesis: glial cells derived from all ependymal cells expressing OPC 1/2/3

Synaptogenesis: before W27 thru birth, requires contact with astrocytes, region dependent (visual cortex done at 8 mo., prefrontal cortex done at 3 yrs)

MECP2: disorder of synaptogenesis - not enough synapses - intellectual impairment, stereotypic hand movements, deceleration of head growth, epilepsy, sleeping problems, breathholding

Question 18

Myelination (when, direction)

What is Palizaeus-Merzbacher disease?

What is Periventricular Leukomalacia?

Answer 18

From birth through adulthood
from posterior to anterior forebrain

P-M: disorder of myelination, mutated PLP1 = nystagmus, hypotonia, stridor (vocal cord paralysis), feeding difficulty, seizures)

PVL: acquired brain injury due to prematurity, subcortical white matter cysts disrupt normal myelin maturation = bleeding, incomplete gyration, ventriculomegaly