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Tracing the functional effects of INSM1 during pancreas development

Abstract:

Insulinoma-associated 1 (INSM1/formally IA-1) is a zinc-finger transcription factor isolated from a human insulinoma subtraction library. Recently, INSM1 has been implicated playing a key role in differentiation of the endocrine pancreas. Pancreatic endocrine-associated target genes, NeuroD/b2 and insulin, were down-regulated by INSM1 through the binding of the target genes' promoter region. In this proposal, we designed a novel transgenic model to analyze the functional effects of INSM1 during pancreas development. A Pdx-1 promoter-specific Tet-on inducible transgenic model will be generated and conditionally expressing INSM1 during pancreas development. The functional effects of the over-expressed INSM1 could be elucidated not only by specific Pdx-1 promoter, but also turn on or off by treatment of doxycycline. Since we will be able to analyze gain of INSM1 function at different stages of pancreas development, these results may provide important insights as how and when the INSM1 functions as a differentiation transcription factor for pancreatic b-cell development.