Pancreatic homeodomain transcription factor IDX1/IPF1 expressed in developing brain regulates somatostatin gene transcription in embryonic neural cells

Hox-like homeodomain proteins play a critical role during embryonic develop ment by regulating the transcription of genes that are important for the ge neration of specific organs or cell types. The homeodomain transcription fa ctor IDX1/IPF1, the expression of which was thought until recently to be re stricted to the pancreas and foregut, is required for pancreas development and for the expression of genes controlling glucose homeostasis. We report that IDX1/IPF1 is also expressed in embryonic rat brain at a time coinciden t with active neurogenesis. Electrophoretic mobility shift assays with nucl ear extracts of embryonic brains indicated that IDX1/IPF1 binds to two soma tostatin promoter elements, SMS-UE-B and the recently discovered SMS-TAAT3, The requirement of these elements for IDX1/IPF1 transactivation of the som atostatin gene in neural cells was confirmed in transfection studies using embryonic cerebral cortex-derived RC2.E10 cells. Immunohistochemical staini ng of rat embryos showed IDX1/IPF1-positive cells located near the ventricu lar surface in germinative areas of the developing central nervous system. Cellular colocalization of IDX1/IPF1 and somatostatin was found in several areas of the developing brain, including cortex, ganglionic eminence, hypot halamus, and inferior colliculus. These results support the notion that IDX 1/IPF1 regulates gene expression during development of the central nervous system independent of its role on pancreas development and function.