Cortical Development

Front 1

Which derivative of the prosencephalon forms the rudiments of the cerebral cortex? When does the differentiation of the prosencephalon occur?

Back 1

*telencephalon
*between embryonic weeks 3 and 8

Front 2

Describe the growth pattern that results in the hemispheric structure of the cortex.

Back 2

*cells on the midline growth plate divide less and show more apoptosis...this results in the fixation of the plate
*cells in the lateral portions proliferate rapidly

Front 3

Name one chemical secreted by organizer tissue that in part directs patterning of the cortex.

Back 3

*sonic hedgehog (SHH)
(*FGf8)

Front 4

Describe the gross defect seen in holoprosencephaly. Deletions in what gene have been implicated as a cause of HPE?

Back 4

*forebrain fails to separate; cortex is continuous as a single holosphere rather than two hemispheres
*SHH in mesencephalon

Front 5

In what part of the developing cortex does cell proliferation occur?

Back 5

Ventricular zone of proliferation, adjacent to the lumen of the brain.

Front 6

What kinds of cells are produced when a neural precursor cell divides symmetrically? When it divides asymmetrically?

Back 6

*symmetric division = 2 glial cells
*assymetric division = 1 neuron + 1 glial cell

Front 7

What are the signs of microcephaly? What is the general defect?

Back 7

*small cortex, MR
*failure to generate the appropriate number of neurons

Front 8

What is ASPM? What do defects in APSM result in? How?

Back 8

*abnormal spindle protein
*microcephaly
*interferes with the organization of spindle fibers in mitotic cells, causing them to arrest in M-phase

Front 9

Mutations in the gene coding for B-catenin have caused what kinds of effects in lab animals? What is the mechanism?

Back 9

*macrocephaly
*enlarged lateral ventricles and an expanded pool of neural precursors

Front 10

When is neural cell fate atleast partially specified?

Back 10

In the paraventricular zone when the neuron is born.

Front 11

Underexpression of GABA neurons can be induced by a specific mutation - what is it?

Back 11

Double mutations to D1x-1/2.

Front 12

What is the difference between radial and tangential migration of neurons?

Back 12

*radial migration: movement along a glial scaffolding system
*tangential migration: movement in a glial-independent manner

Front 13

How are cortical layers laid out - inside-out or outside in?

Back 13

Inside-out, with the deepest layers made first and the most superficial layers made last.

Front 14

What are the 3 general stages in neuron migration?

Back 14

1.Recognition of route and onset of migration
2.Maintenence of migration over long distances
3.Termination of migration at the proper location

Front 15

What is schizencephaly?

Back 15

*defect in neural migration results in random distribution of neurons
*fistula between ventricle and outer surface of brain seen

Front 16

What is the gross appearance of the bain in Type 1 lissencephaly? What causes this defect? What is the mechanism?

Back 16

*smooth cortical surface with no sulci or gyri
*mutation in Lis-1 gene
*abnormal accumulation of microtubules

Front 17

What is the appearance of periventricular hetertopia? What is the primary problem? What symptoms are seen?

Back 17

*enlarged periventricular area
*failure of neurons to initiate migration
*seizures

Front 18

What is the molecular problem in periventricular hetertopia?

Back 18

Mutations in the gene coding for filamin-1 prevent f-actin filaments from binding together normally.

Front 19

Is periventricular hetertopia seen more frequently in boys or girls?

Back 19

It is not seen in boys. The mutation is on an X-linked gene and males are spontaneously aborted. Females survive because they are mosaic carriers.

Front 20

What is the appearance of polymicrogyria?

Back 20

Small gyri inside the cortex.

Front 21

a-3 integrin is proposed to play what role in neural migration? What is the molecular defect seen in knockout animals?

Back 21

*recognition of surroundings during migration
*disruption of f-actin dynamics at the leading edge

Front 22

Reeler mouse mutants have neurons that show an inability to terminate migration at the appropriate location. What is the appearance of these animals' brains?

Back 22

The laminar structure of the cortex is reversed with layer 6 most superficial and layer 1 most deep.

Front 23

How is neural migration affected in Walker-Warburg syndrome? What anatomical anomalies are seen?

Back 23

*neurons fail to terminate migration at the proper location and splay out through the pia mater into the subarachnoid space
*hydrocephaly, thinning of the cortex, aplasia of corpus callosum

Front 24

What is the genetic defect thought to be the cause of Walker-Warburg syndrome?

Back 24

A mutation in the gene coding for mannosyltransferase wich regulates the glycosylation of many proteins.

Front 25

What are the 6 steps in normal cortical development?

Back 25

1.Pattern formation
2.Cell proliferation
3.Cell fate specification
4.Cell migration
5.Cell differentiation
6.Synapse and circuit formation

Front 26

A failure to make the correct synaptic connections generally results in what?

Back 26

Induction of apoptotic pathways.

Front 27

What defect results in neurological separation of the two cortical hemispheres?

Back 27

Agenesis of the corpus callosum.

Front 28

What is tuberus sclerosis? What is a common symptom?

Back 28

*groups of abnormally placed neurons (tubers) make abberent connections with a variety of effects
*epilepsy

Front 29

Fragile X Syndrome results from a mutation in the FMR-1 gene. What are the roles of this gene in normal individuals? There are three.

Back 29

1.Influence the initial generation of a synapse
2.Regulate the generation of NT's and chemotactic factors at the synapse
3.Destroy RNA complexes

Front 30

How does the mutation of FMR-1 seen in Fragile X affect transcription of the gene?

Back 30

*increases the number of CCG repeats in the gene
*this induces methylation of the gene
*transcription is turned off

Front 31

What structural anomalies are seen in Fragile X syndrome?

Back 31

*increase in dendritic spine density
*excess of long, thin spines

Front 32

ARFGEF2 codes for proteins normally involved in vesicular transport of membrane components. What 2 defects are seen when this gene is mutated? What protein is inadequately transported in these patients?

Back 32

1.periventricular hetertopia
2.microcephaly
*B-catenin

Front 33

What are three general effects seen in FAS?

Back 33

1.Increased neuronal apoptosis
2.Sparsity of dendrites
3.Deficits in neuronal growth resulting in loss of brain surface morphology

Front 34

Describe microdysgenesia of the cortex. In what genetic condition is it commonly seen?

Back 34

*abnormal gyrations that protrude through to subcortical layers
*trisomy 21

Front 35

T/F:
The brains of autistic patients are commonly much smaller in volume than normal brains.

Back 35

False: most autistic patients exhibit macrocephaly.

Front 36

Mutations in the neuregulin-1 gene have been implicated in schizophrenia. What is the normal role of this gene?

Back 36

Development of radial glial cells and expression of certain neurotransmitter receptors.

Front 37

T/F:
Cortical development continues into adulthood.

Back 37

This is true.