The carboxyl-terminal domain of Connexin43 is a negative modulator of neuronal differentiation

Marcelo F. Santiago, Pepe Alcami, Katharine M. Striedinger, David C. Spray, Eliana Scemes

Research output: Contribution to journalArticle

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Abstract

Connexin43 (Cx43) is widely expressed in embryonic brain, and its expression becomes restricted mainly to astrocytes as the central nervous system matures. Recent studies have indicated that Cx43 plays important, nonchannel, roles during central nervous system development by affecting neuronal cell migration. Here, we evaluated the effects of Cx43 on neuronal differentiation. For that we used an in vitro model of neural cell development (neurospheres) to evaluate, through immunocytochemistry, electrophysiology, and molecularbiology, the degree of neuronal maturation from neurospheres derived from wild-type (WT) and Cx43-null mice. Our results indicate that Cx43 is a negative modulator of neuronal differentiation. The percent neurospheres containing differentiated neurons and the number of cells displaying inward currents were significantly higher in Cx43-null than in WT littermate neurospheres. Knockdown of Cx43 with small interfering RNA increased the number of WT neurospheres generating differentiated neurons. Blockade of gap junctional communication with carbenoxolone did not induce neuronal differentiation in WT neurospheres. Transfection of Cx43-null neurospheres with Cx43 mutants revealed that Cx43 carboxyl terminus prevents neuronal maturation. In agreement with these in vitro data, in situ analysis of embryonic day 16 brains revealed increased β-III-tubulin expression in germinal zones of Cx43-null compared with that of WT littermates. These results indicate that Cx43, and specifically its carboxyl terminus, is crucial for signaling mechanisms preventing premature neuronal differentiation during embryonic brain development.

Original languageEnglish (US)
Pages (from-to)11836-11845
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number16
DOIs
StatePublished - Apr 16 2010

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Connexin 43
Modulators
Brain
Neurology
Neurons
Central Nervous System
Carbenoxolone
Electrophysiology
Tubulin
Astrocytes
Small Interfering RNA
Embryonic Development
Cell Movement
Transfection
Cell Count
Immunohistochemistry
Communication

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The carboxyl-terminal domain of Connexin43 is a negative modulator of neuronal differentiation. / Santiago, Marcelo F.; Alcami, Pepe; Striedinger, Katharine M.; Spray, David C.; Scemes, Eliana.

In: Journal of Biological Chemistry, Vol. 285, No. 16, 16.04.2010, p. 11836-11845.

Research output: Contribution to journalArticle

Santiago, Marcelo F. ; Alcami, Pepe ; Striedinger, Katharine M. ; Spray, David C. ; Scemes, Eliana. / The carboxyl-terminal domain of Connexin43 is a negative modulator of neuronal differentiation. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 16. pp. 11836-11845.
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