Functional manipulations of acetylcholinesterase splice variants highlight alternative splicing contributions to murine neocortical development

Amir Dori, Jonathan Cohen, William F. Silverman, Yaakov Pollack, Hermona Soreq

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Proliferation and differentiation of mammalian central nervous system progenitor cells involve concertedly controlled transcriptional and alternative splicing modulations. Searching for the developmental implications of this programming, we manipulated specific acetylcholinesterase (AChE) splice variants in the embryonic mouse brain. In wild type mice, 'synaptic' AChE-S appeared in migrating neurons, whereas the C-terminus cleaved off the stress-induced AChE-R variant associated with migratory radial glial fibers. Antisense suppression of AChE-R reduced neuronal migration, allowing increased proliferation of progenitor cells. In contrast, transgenic overexpression of AChE-R was ineffective, whereas transgenic excess of enzymatically active AChE-S or inactive AChE-Sin suppressed progenitors proliferation alone or both proliferation and neuronal migration, respectively. Our findings attribute to alternative splicing events an interactive major role in neocortical development.

Original languageEnglish
Pages (from-to)419-430
Number of pages12
JournalCerebral Cortex
Volume15
Issue number4
DOIs
StatePublished - 1 Apr 2005

Keywords

  • Alternative splicing
  • Neurogenesis
  • Neuronal migration
  • Radial glia
  • Readthrough acetylcholinesterase

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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