The Journal of Membrane Biology

, Volume 245, Issue 5–6, pp 263–273 | Cite as

Cx36 Is a Target of Beta2/NeuroD1, Which Associates with Prenatal Differentiation of Insulin-producing β Cells

  • Rachel Nlend Nlend
  • Aouatef Aït-Lounis
  • Florent Allagnat
  • Valentina Cigliola
  • Anne Charollais
  • Walter Reith
  • Jacques-Antoine Haefliger
  • Paolo Meda
Article

Abstract

The insulin-producing β cells of pancreatic islets are coupled by connexin36 (Cx36) channels. To investigate what controls the expression of this connexin, we have investigated its pattern during mouse pancreas development, and the influence of three transcription factors that are critical for β-cell development and differentiation. We show that (1) the Cx36 gene (Gjd2) is activated early in pancreas development and is markedly induced at the time of the surge of the transcription factors that determine β-cell differentiation; (2) the cognate protein is detected about a week later and is selectively expressed by β cells throughout the prenatal development of mouse pancreas; (3) a 2-kbp fragment of the Gjd2 promoter, which contains three E boxes for the binding of the bHLH factor Beta2/NeuroD1, ensures the expression of Cx36 by β cells; and (4) Beta2/NeuroD1 binds to these E boxes and, in the presence of the E47 ubiquitous cofactor, transactivates the Gjd2 promoter. The data identify Cx36 as a novel early marker of β cells and as a target of Beta2/NeuroD1, which is essential for β-cell development and differentiation.

Keywords

Beta2/neurod1 Connexin Gap junctions Gene regulation Pancreas Promoter Transcription factor 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Rachel Nlend Nlend
    • 1
  • Aouatef Aït-Lounis
    • 4
  • Florent Allagnat
    • 3
  • Valentina Cigliola
    • 1
  • Anne Charollais
    • 1
  • Walter Reith
    • 2
  • Jacques-Antoine Haefliger
    • 3
  • Paolo Meda
    • 1
  1. 1.Department of Cell Physiology and MetabolismUniversity of GenevaGeneva 4Switzerland
  2. 2.Department of Pathology and ImmunologyUniversity of GenevaGeneva 4Switzerland
  3. 3.Department of Internal MedicineUniversity of LausanneLausanneSwitzerland
  4. 4.Laboratory of Cellular and Molecular BiologyUniversity of Algiers, USTHBAlgiersAlgeria

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