BRAIN DEVELOPMENT

NEURAL PLATE FORMATION

• Occurs in day 18-20 (gestational)

• The ectoderm receives signals from the underlying notochord, leading to the formation of the neural plate

• BMP promotes epidermal fate and the inhibition allows for neural differentiation

• Noggin, Chordin and Follistatin all block BMP which ensures neural tissue formation

NEURAL TUBE FORMATION

• Occurs day 21-28

• The neural plate folds into the neural groove, then closes to form the neural tube, which will develop into the brain and spinal cord

• Shh secreted by the notochord helps pattern the ventral neural tube

• BMP assists in patterning the dorsal neural tube

• FGF supports the neural tube in the elongation process

PRIMARY BRAIN VESICLES

• Week 4 

• The neural tube differentiates into three primary brain vesicles

  • Forebrain (Prosencephalon)

  • Midbrain (Mesencephalon)

  • Hindbrain (Rhombencephalon)

• Shh defines ventral brain structures

• Wnt is involved in dorsal brain structures

• Retinoic Acid helps regional specification 

NEUROGENESIS

• Occurs in week 5 and onward

• Neural stem cells divide and differentiate into neurons

• Notch is a key regulator in the fate of stem cells

• Neurogenin promotes neuron formation

• BDNF (Brain-Derived Neurotrophic Factor) supports the neuron survival

GLIAL CELL DEVELOPMENT

• Glial cells such as astrocytes, oligodendrocytes and microglia emerge to support neurons

• EGF (epidermal Growth Factor) promotes glial proliferation 

• PDGF (Platelet-Derived Growth Factor supports oligodendrocyte development

SYNAPSE FORMATION

• This occurs in the late fetal stage and postnatal 

• Neurons extend axons and dendrites, forming synaptic connections

• Myelination occurs after the synapse has been formed

• Neurexins and Neuroligins help the synapse formation

HOW WNT SIGNALING PLAYS A ROLE IN NEUROGENESIS

• Sustained Wnt signaling showed to delayed the onset of neurogenic transcription factors such as Pax6 and Tbr2, which slowed neurogenesis

• The loss of Wnt signaling accelerates the expression of the neurogenic factors and promotes neuronal differentiation

• In the cerebral cortex if Wnt is persistent then it leads to the formation of hippocampal-like cells instead of neurons.

HOLOPROSENCEPHALY

• Occurs when the forebrain fails to divide properly into the two distinct hemispheres 

• Disruptions in the Shh

• Can be a result form mutations in TGIF1 and TGIF 2 which lead to a disruption in  the Wnt pathway

EPILEPSY

• The disruption in the Wnt/β-catenin pathway has shown to be a cause in temporal lobe epilepsy

• Due to the Wnt pathway playing a role in neurogenesis disruptions which can lead to malfunctioning neurons

SCHIZENCEPHALY

• Rare brain malformation caused by a congenital neuronal migration disorder

• Characterized by a full thickness cleft lined with heterotopic gray matter and filled with CSF

• Caused by a disruption in Shh pathway