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.