The Ectopic Expression of Pax4 in the Mouse Pancreas Converts Progenitor Cells into Alpha and Subsequently Beta Cells

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Aug 12

PMID 19665969

Citations 298

Authors

Patrick Collombat

Xiaobo Xu

Philippe Ravassard

Beatriz Sosa-Pineda

Sebastien Dussaud

Nils Billestrup

Ole D Madsen

Palle Serup

Harry Heimberg

Ahmed Mansouri

Affiliations

Soon will be listed here.

Abstract

We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed alpha cells fail to correct the hypoglucagonemia since they subsequently acquire a beta cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.

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