Interplay between electrical activity and bone morphogenetic protein signaling regulates spinal neuron differentiation

Immani Swapna, Laura N Borodinsky

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

A gradient of bone morphogenetic proteins (BMPs) along the dorsoventral axis of the spinal cord is necessary for the specification of dorsal neurons. Concurrently, a gradient of calcium-mediated electrical activity is present in the developing spinal cord but in an opposing ventrodorsal direction. Whether BMPs and electrical activity interact in embryonic spinal neurons remains unknown. We show that BMP decreases electrical activity by enhancing p38 MAPK-mediated negative modulation of voltage-gated sodium channels. In turn, electrical activity affects the phosphorylation status and nuclear level of activated Smads, the canonical components of BMP signaling. This interaction between calcium spike activity and BMP signaling regulates the specification of the dorsal commissural spinal neuron phenotype. The present study identifies an unexpected interplay between BMPs and electrical activity that is critical for decoding the morphogen gradient during spinal neuron differentiation.

Original languageEnglish (US)
Pages (from-to)16336-16341
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number40
DOIs
StatePublished - Oct 2 2012

Keywords

  • Activity-dependent neuronal specification
  • Calcium signaling
  • Mitogen-activated protein kinase
  • Noggin
  • Spinal interneuron

ASJC Scopus subject areas

  • General

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