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First published online 3 December 2003
doi: 10.1242/dev.00921

Development 131, 165-179 (2004)
Published by The Company of Biologists 2004
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Global expression analysis of gene regulatory pathways during endocrine pancreatic development

Guoqiang Gu1,*,{ddagger}, James M. Wells1,{dagger},{ddagger}, David Dombkowski2, Fred Preffer2, Bruce Aronow{dagger} and Douglas A. Melton1,§

1 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
2 Department of Pathology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA

§ Author for correspondence (e-mail: dmelton{at}biohp.harvard.edu)

Accepted 30 September 2003

To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate {alpha}, ß and {delta} cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.

Key words: Myt1, endoderm, Pancreas, Endocrine, Islets, Microarray






© The Company of Biologists Ltd 2004