Ngn3 (neurogenin 3) is a bHLH transcription factor expressed in the pancreatic endocrine precursor cells. Ngn3 mRNA is found in the developing pancreas between day 9 and 18.5 of gestation. Expression of ngn3 is extinguished in differentiated islet alpha and beta cells, as it never co-localizes with glucagon or insulin. Homozygous null mice for Ngn3 develop severe diabetes and die 2-3 days after birth. No islet of Langerhans are present in the pancreas in these mutant animals. Thus, Ngn3 is absolutely essential for the pancreatic endocrine cell development and it is also the earliest marker for endocrine precursor cells. The following specific aims will be pursued through this proposal: 1) To generate a Ngn3-GFP mouse by homologous recombination to be used in lineage tracing study and for the purification and culture of endocrine stem cells. 2) To identify early and late target genes of Ngn3 using microarray technology.
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