Intracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling

Dev Cell. 2018 May 21;45(4):512-525.e5. doi: 10.1016/j.devcel.2018.04.013. Epub 2018 May 10.


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; intracellular calcium release; ryanodine receptors; tissue pattering.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Patterning
  • Calcium / metabolism*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / physiology*
  • Gene Expression Regulation, Developmental*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Morphogenesis
  • Muscles / cytology
  • Muscles / metabolism
  • Neural Tube / cytology
  • Neural Tube / metabolism
  • Signal Transduction*
  • Somites / cytology
  • Somites / metabolism*
  • Zebrafish / embryology
  • Zebrafish / physiology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • Hedgehog Proteins
  • Zebrafish Proteins
  • Calcium