Abstract
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, beta 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.
Highlights
The vertebrate pancreas has two functions: producing digestive enzymes, and regulating glucose homeostasis
A comparison of the transcriptional profile of neurogenin 3 (NGN3) + cells with NGN3– cells was aimed at distinguishing the endocrine and exocrine compartments of the embryonic pancreas
We found that 47, 38, 35 and 46% of the genes present on the microarrays are expressed in the E7.5 endoderm, E10.5 pancreatic progenitor cells, E13.5 endocrine precursors, and islets of Langerhans, respectively
Summary
The vertebrate pancreas has two functions: producing digestive enzymes (exocrine), and regulating glucose homeostasis (endocrine). These separate functions are reflected in the complex architecture of the pancreas. The endocrine islets contain four types of cells that secrete hormones to regulate glucose metabolism and other physiological processes (Slack, 1995). The developing pancreas presents a challenge for developmental biologists because of the complex morphogenetic processes underlying development of this organ. Type I or insulin dependent diabetes mellitus results from the autoimmune-mediated destruction of insulin-secreting β cells in islets, emphasizing the importance of understanding pancreas and β cell development (Mathis et al, 2001; Tisch and McDevitt, 1996)
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