Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia

Pax genes are important developmental regulators and function at multiple s tages of vertebrate kidney organogenesis. In this report, we have used the zebrafish pax2.1 mutant no isthmus to investigate the role for pax2.1 in de velopment of the pronephros. We demonstrate a requirement for pax2.1 in mul tiple aspects of pronephric development including tubule and duct epithelia l differentiation and cloaca morphogenesis. Morphological analysis demonstr ates that noi(-) larvae specifically lack pronephric tubules while glomerul ar cell differentiation is unaffected. In addition, pax2.1 expression in th e lateral cells of the pronephric primordium is required to restrict the do mains of Wilms' tumor suppressor (wt1) and vascular endothelial growth fact or (VEGF) gene expression to medial podocyte progenitors. Ectopic podocyte- specific marker expression in pronephric duct cells correlates with loss of expression of the pronephric tubule and duct-specific markers mAb 3G8 and a Na+/K+ ATPase alpha 1 subunit. The results suggest that the failure in pr onephric tubule differentiation in noi arises from a patterning defect duri ng differentiation of the pronephric primordium and that mutually inhibitor y regulatory interactions play an important role in defining the boundary b etween glomerular and tubule progenitors in the forming nephron.