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Calcium dynamics at the neural cell primary cilium regulate Hedgehog signaling-dependent neurogenesis in the embryonic neural tube.
Shim, Sangwoo; Goyal, Raman; Panoutsopoulos, Alexios A; Balashova, Olga A; Lee, David; Borodinsky, Laura N.
Affiliation
  • Shim S; Department of Physiology and Membrane Biology, University of California Davis, Sacramento, CA 95817.
  • Goyal R; Shriners Hospital for Children, University of California Davis, Sacramento, CA 95817.
  • Panoutsopoulos AA; Department of Physiology and Membrane Biology, University of California Davis, Sacramento, CA 95817.
  • Balashova OA; Shriners Hospital for Children, University of California Davis, Sacramento, CA 95817.
  • Lee D; Department of Physiology and Membrane Biology, University of California Davis, Sacramento, CA 95817.
  • Borodinsky LN; Shriners Hospital for Children, University of California Davis, Sacramento, CA 95817.
Proc Natl Acad Sci U S A ; 120(23): e2220037120, 2023 06 06.
Article in En | MEDLINE | ID: mdl-37252980
ABSTRACT
The balance between neural stem cell proliferation and neuronal differentiation is paramount for the appropriate development of the nervous system. Sonic hedgehog (Shh) is known to sequentially promote cell proliferation and specification of neuronal phenotypes, but the signaling mechanisms responsible for the developmental switch from mitogenic to neurogenic have remained unclear. Here, we show that Shh enhances Ca2+ activity at the neural cell primary cilium of developing Xenopus laevis embryos through Ca2+ influx via transient receptor potential cation channel subfamily C member 3 (TRPC3) and release from intracellular stores in a developmental stage-dependent manner. This ciliary Ca2+ activity in turn antagonizes canonical, proliferative Shh signaling in neural stem cells by down-regulating Sox2 expression and up-regulating expression of neurogenic genes, enabling neuronal differentiation. These discoveries indicate that the Shh-Ca2+-dependent switch in neural cell ciliary signaling triggers the switch in Shh action from canonical-mitogenic to neurogenic. The molecular mechanisms identified in this neurogenic signaling axis are potential targets for the treatment of brain tumors and neurodevelopmental disorders.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium / Xenopus Proteins / Hedgehog Proteins Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2023 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium / Xenopus Proteins / Hedgehog Proteins Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2023 Type: Article