CNS and Brain Development Flashcards
In specification of the dorsoventral axis, where do sensory and motor neurons sit?
Sensory neurons go into the dorsal spinal cord.
Motor neurons sit ventrally.
What is the Sonic Hedgehog morphogen secreted by?
The notochord
What is secretion of Shh by the notochord required for?
Development of midline structures
What is highly conserved in the notochord?
Expression of Shh
What does the expression of Shh in the notochord determine?
Cell fate as you move from ventral to dorsal through the neural tube
Give the reading on specification of the dorso-ventral axis.
Engrailed gene is also thought to play a role in dorsoventral patterning.
Limbs of mice lacking Engrailed showed a double-dorsal phenotype.
Engrailed acts to define ventral ectodermal identity.
In which species was Shh first identified?
Drosophila melanogaster
Dissected neural tube was cultured in different concentrations of Shh.
How did this impact neuronal identity?
High concentrations of Shh - became almost all motor neurons.
With anti-Shh to block Shh action - no neuronal cells were produced.
What are the two roles of Shh in CNS and brain development?
- Specification of the dorso-ventral axis
- Neuronal identity
Give the reading for Shh and neuronal identity.
- Progenitor cells either Nkx2.2 or Pax6 in response to graded Shh signalling,
- Mice lacking Pax6, progenitor cells generated neurons characteristic of high Shh activity.
- Pax6 controls neuronal pattern indirectly.
What do different combinations of transcription factors define?
Progenitor cell populations in the ventral neural tube
When different transcription factors are overlaid, what does this create?
Different types of neurons
How does Sox2 function?
To maintain neural progenitor identity.
Give the extra reading for transcriptional definition of progenitor domains.
- SOX2 functions to maintain neural progenitor identity.
- Expression of SOX2 inhibits neuronal differentiation and results in maintenance of progenitor characteristics.
- Inhibition results in onset of early neuronal differentiation markers.
What are Robo and Slit essential for?
The formation of commissures
Why do bodies need a sense of left and right side from commissures?
For sensory processing and locomotion
What animal is used to understand commissure formation?
How?
Drosophila
Nerves stained with antibodies
Explain how Robo and Slit lead to the formation of commissures.
- Axon expressing Robo is repelled by Slit and grows longitudinally
- Robo is down-regulated, and the axon is no longer sensitive to Slit at the midline
- The axon crosses over
- Robo is up-regulated, and the axon remains on the colateral side.
What happens in Robo mutants?
Axons cross and recross at the midline because they are insensitive to Slit
What happens in Slit mutants?
Axon tracts collapse to the midline of the body and only respond to attractive signals
