Intracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling

Developmental Cell
Dana Klatt ShawDavid Jonah Grunwald

Abstract

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.

Citations

May 21, 2019·Human Molecular Genetics·Stephanie BrennanRobert T Dirksen
Dec 4, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Francisco HuizarJeremiah Zartman
Aug 7, 2019·Disease Models & Mechanisms·Alexis A ChagovetzDavid J Grunwald
Feb 26, 2021·EMBO Reports·Maya Emmons-Bell, Iswar K Hariharan
Apr 7, 2021·Journal of Medical Genetics·Ichrak DrissiGeoff Woods

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