<i>Kif3a</i> Controls Murine Nephron Number Via GLI3 Repressor, Cell Survival, and Gene Expression in a Lineage-Specific Manner

<div><p>The primary cilium is required during early embryo patterning, epithelial tubulogenesis, and growth factor-dependent signal transduction. The requirement for primary cilia during renal epithelial-mesenchymal tissue interactions that give rise to nephrons is undefined. Here, we used <i>Cre-</i>mediated recombination to generate mice with <i>Kif3a</i> deficiency targeted to the ureteric and/or metanephric mesenchyme cell lineages in the embryonic kidney. Gradual loss of primary cilia in either lineage leads to a phenotype of reduced nephron number. Remarkably, in addition to cyst formation, loss of primary cilia in the ureteric epithelial cell leads to decreased expression of <i>Wnt11</i> and <i>Ret</i> and reduced ureteric branching. Constitutive expression of GLI3 repressor (<i>Gli3<sup>Δ699/+</sup></i>) rescues these abnormalities. In embryonic metanephric mesenchyme cells, <i>Kif3a</i> deficiency limits survival of nephrogenic progenitor cells and expression of genes required for nephron formation. Together, our data demonstrate that <i>Kif3a</i> controls nephron number via distinct cell lineage-specific mechanisms.</p></div>