Developmental Cell
Volume 45, Issue 4, 21 May 2018, Pages 512-525.e5
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Article
Intracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling

https://doi.org/10.1016/j.devcel.2018.04.013Get rights and content
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Highlights

  • RyR-mediated intracellular Ca2+ release modifies Shh-dependent tissue patterning

  • Loss or gain of RyR activity modulates gene expression in response to Shh ligand

  • Precursors with reduced RyR function adopt fates reflecting diminished signaling

  • RyR calcium release channels are required in the Shh ligand-receiving cell

Summary

Graded Shh signaling across fields of precursor cells coordinates patterns of gene expression, differentiation, and morphogenetic behavior as precursors form complex structures, such as the nervous system, the limbs, and craniofacial skeleton. Here we discover that intracellular calcium mobilization, a process tightly controlled and readily modulated, regulates the level of Shh-dependent gene expression in responding cells and affects the development of all Shh-dependent cell types in the zebrafish embryo. Reduced expression or modified activity of ryanodine receptor (RyR) intracellular calcium release channels shifted the allocation of Shh-dependent cell fates in the somitic muscle and neural tube. Mosaic analysis revealed that RyR-mediated calcium mobilization is required specifically in Shh ligand-receiving cells. This work reveals that RyR channels participate in intercellular signal transduction events. As modulation of RyR activity modifies tissue patterning, we hypothesize that alterations in intracellular calcium mobilization contribute to both birth defects and evolutionary modifications of morphology.

Keywords

hedgehog signaling
tissue pattering
intracellular calcium release
ryanodine receptors

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