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First published online 30 September 2009
doi: 10.1242/dev.039214

Development 136, 3567-3574 (2009)
Published by The Company of Biologists 2009
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Pancreatic neurogenin 3-expressing cells are unipotent islet precursors

Renaud Desgraz and Pedro L. Herrera*

Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel-Servet, 1211 Geneva-4, Switzerland.

* Author for correspondence (pedro.herrera{at}unige.ch)

Accepted 27 August 2009

Pancreatic islet endocrine cells arise during development from precursors expressing neurogenin 3 (Ngn3). As a population, Ngn3+ cells produce all islet cell types, but the potential of individual Ngn3+ cells, an issue central to organogenesis in general and to in vitro differentiation towards cell-based therapies, has not been addressed. We performed in vivo clonal analyses in mice to study the proliferation and differentiation of very large numbers of single Ngn3+ cells using MADM, a genetic system in which a Cre-dependent chromosomal translocation labels, at extremely low mosaic efficiency, a small number of Ngn3+ cells. We scored large numbers of progeny arising from single Ngn3+ cells. In newborns, labeled islets frequently contained just a single tagged endocrine cell, indicating for the first time that each Ngn3+ cell is the precursor of a single endocrine cell. In adults, small clusters of two to three Ngn3+ progeny were detected, but all expressed the same hormone, indicating a low rate of replication from birth to adult stages. We propose a model whereby Ngn3+ cells are monotypic (i.e. unipotent) precursors, and use this paradigm to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans.

Key words: Cell lineage, Clonal analysis, Islet, Mosaic, Progenitor, Transgenic, Mouse


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Development 2009 136: e2103. [Full Text]  





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