Early Brain Development

Question 1

Steps of Early Brain Development

Answer 1

1. Neuronal induction
2. Compartmentalization/Patterning
3. Neurogenesis & Neuron migration
4. Outgrowth of axons
5. Synapse formation & Refinement
6. Activity-dependent synaptic rearrangment

Question 2

Gastrulation

Answer 2

Blastophore (small slit-like infolding on future dorsal site)
Mesoderm & Endoderm move under the slit through blastopore –> Involution
Creation of a new internal cavity –> Arcehnteron

Question 3

Neural inducers

Answer 3

Chordin, Noggin, Folistatin
BMPs that activate Smad & zic1 induce ectoderm to become epidermal tissue –> Neural inducers block this induction –> Ecotderm = neural

Question 4

Graded signals

Answer 4

Wnt signaling at the dorsal site of the neural tube
Sonic hedhog (SHH): Ventral patterning signal –> Induces florr plate –> Blockage can create cyclops
Holoprosencephaly: Genetic lesions in SHH signaling –> Progressivee loss of neurons from ventral lesions

Question 5

Rhombomeres

Answer 5

Similar pattern of neuronal cell types develop along AP axis of each rhombomere
Each rhombomere aquiers unique identity (Cranial nerves)
Expression of Hox genes coincides with rhondomere boundaries

Question 6

Lateral inhibition

Answer 6

If one cell expresses the given trait (=Neuroblast) –> Neighbouring cells are switched off via Delta-Notch signaling –> Less Notch = Neural fate, High notch = Epidermal fate

Question 7

Human cortical development vs. other animals

Answer 7

5 supgranular neuron types
Large modified pyramidal neurons
Unique subtypes of interneurons
3 classes of astrocytes
Rosehip cells –> Inhibitor

–> Human cortical development is protracted, complex & cellularly more diverse
Developing human subventricular zone has massively expanded outer region (Size & complexitiy)

Question 8

Patterning

Answer 8

Area patterning –> Functionally unique subdivision with different cryoarchitecture
Laminar patterning –> 6 radially organized layer

Question 9

Inside-development of the cortex

Answer 9

Neurons of the deepest layer are generated in early stages, upper layers in late stages –> Each wave of neurons migrates past those in existing cortical plate

Question 10

Radial unit hypothesis

Answer 10

Neurons migrate along radial glia fibers to reach the cortical plate
Outer radial glia (oRG) –> No connection to ventricular zone (in OSVZ)
Ventricular radial glia (vRG) -> Connected to ventricular zone

Question 11

Continous scaffold stage (RUH)

Answer 11

Symmetric self-renewing divisions of vRG expand founder population –> Additional cortical columns & tengential expansion
Discontinous scaffold stage: Radial glial to discontinous structure –> tRG & oRG
Self-renewing divisions for tangential expansion
Neurogenic divisions for radial expansion

Question 12

Human lisencephaly

Answer 12

Defect in cortical development
Brain appears smooth –> Altered lamination

Question 13

Genes for cortical development

Answer 13

Human-specific gene expression changes during development: Compare via organoids human & primates
ARHGAP113: Human specific gene that is enriched in cortical tRG & oRG, lacks mouse orthologue –> May cause neocortex expansion