S08-06 Antagonistic interactions between canonical and non-canonical wnt signals regulate morphogenesis of the embryonic kidney

The kidney and vasculature are intimately linked functionally and during development, where nephric and blood/vascular progenitor cells occupy adjacent bands of mesoderm in zebrafish and frog embryos. Developmental mechanisms underlying the differentiation of kidney vs. blood/vascular lineages are unknown. The odd skipped related1 (osr1) gene encodes a zinc finger transcription factor that is expressed in the germ ring mesendoderm and subsequently in the endoderm and intermediate mesoderm, prior to the expression of definitive kidney or blood/vascular markers. Knockdown of osr1 in zebrafish embryos resulted in a segmentspecific loss of anterior kidney progenitors and a compensatory increase in the number of angioblast cells in the same trunk region. Kidney glomeruli and proximal tubules were absent while the cardinal vein and posterior venous plexuswere expanded. Altered kidney vs. vascular development correlated with expanded endoderm development in osr1 knockdowns. Combined osr1 loss of function with blockade of endoderm development by knockdown of sox32/ casanova rescued kidney proximal tubule but not glomerular development. Absence of glomerular development correlated with osr1 co-expression with wt1 in podocyte progenitor cells. The results indicate that osr1 affects kidney proximal tubule and angioblast development by a non-cell autonomous effect mediated by endoderm while glomerular development is likely to be due to a cell-autonomous role for osr1 in podocyte progenitors.