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Hox-like homeodomain proteins play a critical role during embryonic development by regulating the transcription of genes that are important for the generation of specific organs or cell types. The homeodomain transcription factor IDX1/IPF1, the expression of which was thought until recently to be restricted 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 coincident with active neurogenesis. Electrophoretic mobility shift assays with nuclear extracts of embryonic brains indicated that IDX1/IPF1 binds to two somatostatin promoter elements, SMS-UE-B and the recently discovered SMS-TAAT3. The requirement of these elements for IDX1/ IPF1 transactivation of the somatostatin gene in neural cells was confirmed in transfection studies using embryonic cerebral cortex-derived RC2.E10 cells. Immunohistochemical staining of rat embryos showed IDX1/IPF1-positive cells located near the ventricular 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, hypothalamus, and inferior colliculus. These results support the notion that IDX1/IPF1 regulates gene expression during development of the central nervous system independent of its role on pancreas development and function.Homeodomain genes encode a large family of transcription factors that are grouped in different classes, including, for example, Hox-, POU-, Pax-, LIM-, and Dlx-like proteins, depending on the relative degree of conservation of the homeodomain. During gestation, expression of individual homeodomain genes is critical for proper regional development of the central nervous system (CNS) 1 and peripheral tissues of the embryo. IDX1/IPF1 (also known as STF-1 and PDX-1) is a transcription factor encoded by a Hox-like homeodomain gene, the expression of which was initially described to be restricted to the pancreas and duodenum, and it has been demonstrated that pancreas development requires IDX1/IPF1 in mice (1, 2). This requirement was confirmed in the human by the identification of an individual with pancreatic agenesis and a homozygous mutation in the IPF-1 gene (3). In addition, IDX1/IPF1 is essential for normal pancreatic islet function by regulating the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, and glucose transporter type 2 (4 -8). Importantly, in humans, heterozygous mutations of the IPF-1 gene are linked to a type of autosomal dominant diabetes mellitus known as maturity onset diabetes of the young (MODY4) (9).In the developing neural tube, different homeodomain genes that control mechanisms of regional and cellular determination are selectively expressed in the primordia of the three major regions of the CNS: forebrain, midbrain, and hindbrain (10). In the hindbrain, certain Hox-like ...

Expression of the homeodomain transcription factor IDX1/IPF1 has been shown to be restricted to cells in the developing foregut that form the pancreatic primordium. In the adult, IDX1/IPF1 is expressed in the duodenum and pancreatic islets. The IDX1/IPF1 gene is required for pancreatic development, and in the human, heterozygous mutations have been linked to diabetes mellitus. In the present communication, we report that IDX1/IPF1 is expressed in discrete cells of the rat central nervous system during embryonic development. Using RT-PCR, IDX1/IPF1 mRNA was detected in neural precursor RC2.E10 cells, as well as in both forebrain and hindbrain of developing rats at embryonic day 15 (E15). The presence of IDX1/IPF1 protein was confirmed by Western immunoblotting. Immunohistochemical analyses of sagittal sections of E15 rats demonstrated the presence of scattered IDX1/IPF1-immunopositive cells in the forebrain. Finally, electrophoretic mobility shift assays using nuclear extracts from neural cells revealed the presence of IDX1/IPF1 bound to a putative homeodomain protein DNA-binding site present in the promoter of the glial fibrillary acidic protein gene. Our results suggest that IDX1/IPF1 may have previously unsuspected extrapancreatic functions during development of neural cells in the central nervous system.