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#Shh signaling

3 public questions tagged with this topic.

chick development-l

Sonic hedgehog (Shh) signaling during chick development is crucial for:

Sonic hedgehog secreted from Hensen's node and left paraxial mesoderm plays pivotal role in left-right asymmetry, not just dorsoventral neural patterning. Shh induces Caronte, a Cerberus family BMP antagonist, on left side near node. Caronte inhibits BMP signaling locally, relieving BMP-mediated repression of Nodal in left lateral plate mesoderm via FoxH1 transcription. Right side FGF8 maintains BMP activity blocking Nodal. This Shh-Caronte-Nodal-Pitx2 cascade drives heart looping and gut coiling. Loss of asymmetric Shh randomizes situs, demonstrating crucial role in left-right asymmetry specification beyond neural tube closure.

Ref: Levin, Cell 1995; Gilbert, Developmental Biology, Chapter 12: Sonic hedgehog signaling in left-right asymmetry regulation.

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Fertilization in mammals-lll

Shh signaling blocked by:

Sonic hedgehog signaling involves cholesterol-modified ligand binding Patched relieving inhibition of Smoothened GPCR-like protein, activating GLI transcription for ventral patterning, limb bud and organogenesis. Cyclopamine is steroidal alkaloid from Veratrum californicum acting as Smoothened antagonist, binding transmembrane domain preventing downstream GLI activation. Ingestion during pregnancy causes holoprosencephaly and cyclopia in lambs. Alcohol, BPA and retinoic acid teratogens act via different pathways: alcohol disrupts L1CAM and Shh indirectly, BPA via estrogen receptors, retinoic acid via HOX dysregulation. Cyclopamine is canonical specific chemical probe that experimentally blocks Shh, used to model Shh deficiency disorders and study morphogen gradients.

Ref: Chen et al., Genes Dev 2002: Cyclopamine inhibition of Smoothened blocks Sonic hedgehog signaling in developmental patterning.

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