Sonic hedgehog in temporal control of somite formation

Area of Science:

• Developmental Biology
• Molecular Biology
• Embryology

Background:

• Vertebrate embryonic development relies on precise temporal control of somite formation.
• The presomitic mesoderm (PSM) utilizes a molecular clock for segmentation, previously thought to be independent of midline signaling.
• Sonic hedgehog (Shh) from the notochord's role in this temporal control was not fully understood.

Purpose of the Study:

• To investigate the contribution of notochord-derived signaling, specifically Shh, to the temporal regulation of somitogenesis.
• To analyze the effects of notochord ablation on somite formation rate and molecular clock gene expression.
• To elucidate the molecular mechanisms by which notochord signaling influences PSM segmentation.

Main Methods:

• Surgical notochord ablation in chick embryos.
• Assessment of somite formation rate and number.
• Analysis of somitogenesis clock gene expression oscillations.
• Pharmacological inhibition and exogenous supply of Shh.
• Gene expression analysis of Shh pathway components (patched1, smoothened, gli1, gli2, gli3) and retinoic acid pathway (raldh2).
• Supplementation with retinoic acid (RA).

Main Results:

• Notochord ablation delayed somite formation and increased the period of clock gene oscillations.
• Shh signaling inhibition mimicked these effects, while Shh supply rescued them.
• Notochord ablation altered the expression of Shh pathway components and raldh2.
• Exogenous RA supplementation rescued the effects of notochord ablation on somite formation.
• A model suggests Shh and RA pathways converge to inhibit Gli activity in the PSM.

Conclusions:

• Notochord-derived Shh signaling is essential for regulating the pace of the somitogenesis clock.
• A balance between Shh and retinoic acid pathways ensures robust and timely somite formation.
• The notochord is an integral component of the molecular network controlling embryonic segmentation timing.