Cx36 is a target of Beta2/NeuroD1, which associates with prenatal differentiation of insulin-producing β cells.
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.
Department of Cell Physiology and Metabolism, University of Geneva, CMU, 1 Rue Michel Servet CH- 1211, Geneva 4, Switzerland.
Rachel Nlend
RN
Nlend
Aouatef
A
Aït-Lounis
Florent
F
Allagnat
Valentina
V
Cigliola
Anne
A
Charollais
Walter
W
Reith
Jacques-Antoine
JA
Haefliger
Paolo
P
Meda
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097004:Gap Junction delta-2 Protein
D051792:Basic Helix-Loop-Helix Proteins; D017630:Connexins; D000097004:Gap Junction delta-2 Protein; C501008:Neurod1 protein, mouse