The basic-helix-loop-helix protein Pod1 is critically important for kidneyand lung organogenesis

Epithelial-mesenchymal interactions are required for the development of all solid organs but few molecular mechanisms that underlie these interactions have been identified. Pod1 is a basic-helix-loop-helix (bHLH) transcriptio n factor that is highly expressed in the mesenchyme of developing organs th at include the lung, kidney, gut and heart and in glomerular visceral epith elial cells (podocytes). To determine the function of Pod1 in vivo, we have generated a lacZ-expressing null Pod1 allele, Null mutant mice are born bu t die in the perinatal period with severely hypoplastic lungs and kidneys t hat lack alveoli and mature glomeruli, Although Pod1 is exclusively express ed in the mesenchyme and podocytes, major defects are observed in the adjac ent epithelia and include abnormalities in epithelial differentiation and b ranching morphogenesis. Pod1 therefore appears to be essential for regulating properties of the mes enchyme that are critically important for lung and kidney morphogenesis. De fects specific to later specialized cell types where Pod1 is expressed, suc h as the podocytes, were also observed, suggesting that this transcription factor may play multiple roles in kidney morphogenesis.