POD-1, A MESODERM-SPECIFIC BASIC-HELIX-LOOP-HELIX PROTEIN EXPRESSED IN MESENCHYMAL AND GLOMERULAR EPITHELIAL-CELLS IN THE DEVELOPING KIDNEY

Basic-helix-loop-helix (bHLH) proteins are transcriptional regulatory proteins that govern cell fate determination and differentiation in a variety of tissues. We have identified a novel bHLH protein, named Pod -1, that belongs to a recently-described subfamily of bHLH proteins th at have essential roles in the embryonic development of mesodermal tis sues. In the adult human and mouse, Pod-1 was most highly expressed in the kidney, lung and heart. In developing mouse embryos, Pod-1 was se lectively expressed in mesenchymal cells at sites of epithelial-mesenc hymal interaction in the kidney, lung, intestine and pancreas. Pod-1 w as also expressed in visceral glomerular epithelial cells (podocytes) in the kidney, and its expression coincided with the onset of podocyte differentiation. The expression of Pod-1 in embryonic kidney explants was inhibited using antisense oligonucleotides. Inhibition of Pod-1 e xpression resulted in decreased mesenchymal cell condensation around t he ureteric bud and a 40% decrease in ureteric branching. Pod-1 is the first tissue-restricted basic-helix-loop-helix protein that has been identified in the developing kidney where it may play a role in the re gulation of morphogenetic events. (C) 1998 Elsevier Science Ireland Lt d.