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#neural tube patterning

3 public questions tagged with this topic.

Morphogen Induction-l

Which transcription factor is essential for specifying neural tube patterning along the dorsal-ventral axis?

Ventral neural tube patterning relies on Sonic hedgehog morphogen interpreted through Gli transcription factors, particularly Gli2 activator and Gli3 repressor forms, to establish nested expression of homeodomain proteins forming progenitor code. Shh gradient represses Class I factors Pax6, Dbx1, Irx3 ventrally and induces Class II factors Nkx2.2, Olig2, Nkx6.1 in threshold-dependent manner. Cross-repressive interactions between classes sharpen boundaries creating five ventral progenitor domains that generate distinct interneuron and motor neuron subtypes essential for circuitry. Sox2 maintains neural progenitors, Nanog and Oct4 regulate pluripotency not dorsoventral patterning. Therefore Shh signaling through Gli is central specifier.

Ref: Briscoe and Small, Development 2015, Shh-Gli Code in Neural Tube Patterning.

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Induction Morphogen -ll

Which signaling molecule is responsible for specifying neural tube patterning along the dorsal-ventral axis?

Ventral neural tube identity is controlled by Sonic hedgehog secreted from notochord and floor plate. Shh diffuses dorsally establishing a ventral-to-dorsal gradient that antagonizes dorsal BMP and Wnt signals from roof plate. Different thresholds activate graded transcription factor codes: high Shh induces Nkx2.2 and floor plate genes, intermediate induces Olig2 and motor neurons, low induces Pax6 and interneurons. Gli activator-repressor ratio translates Shh dose into position-specific gene expression, compartmentalizing motor neuron, V0-V3 interneuron domains along dorsoventral axis essential for functional spinal cord circuitry and locomotor output.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 13: Neural Tube Dorsoventral Patterning by Shh.

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Paracrine Factor

Which of the following Hedgehog proteins is primarily responsible for neural tube patterning?

Sonic hedgehog patterning vertebrate central nervous system is classic morphogen gradient regulated by cholesterol and palmitate modifications restricting diffusion. Secreted from notochord and floor plate, cholesterol-modified Shh diffuses dorsally forming ventral-high dorsal-low gradient, binding Patched on neuroepithelial progenitors reducing Gli repressor formation via Smoothened derepression and PKA inhibition. High concentration inhibits Gli3R, activating Nkx2.2, Olig2 for V3 and motor neurons, intermediate concentrations activate Dbx, Pax6 for interneurons. Indian hedgehog regulates bone growth plate chondrocytes, Desert supports spermatogenesis, but only Sonic establishes ventral neural tube identities demonstrated by Shh knockout dorsalization and holoprosencephaly phenotype.

Ref: Jessell, Nature Reviews Neuroscience 2000: Sonic hedgehog as ventral neural tube morphogen patterning motor neurons.

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