biostudies-literature00480Klatt Shaw DNICHD NIH HHSNINDS NIH HHSNIGMS NIH HHS512-525.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC6007892biostudies-literatureUnknown45(4)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.Developmental cellIntracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling.PMC6007892R03 NS071415R01 HD081950R21 HD065169T32 GM007464T32 HD007491Grunwald DJRitchie EGunther DJurynec MJKlatt Shaw DChagovetz AA48falseIntracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling.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.2018-01-01T00:00:00Z2018 May2020-10-31T09:23:50Z2019-06-06T23:20:56ZS-EPMC60078922975480210.1016/j.devcel.2018.04.013