title: Kif3a controls murine nephron number via GLI3 repressor, cell survival, and gene expression in a lineage-specific manner.
abstract: 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 Cre-mediated recombination to generate mice with Kif3a 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 Wnt11 and Ret and reduced ureteric branching. Constitutive expression of GLI3 repressor (Gli3(Δ699/+) ) rescues these abnormalities. In embryonic metanephric mesenchyme cells, Kif3a deficiency limits survival of nephrogenic progenitor cells and expression of genes required for nephron formation. Together, our data demonstrate that Kif3a controls nephron number via distinct cell lineage-specific mechanisms.
authors.affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lijun
authors.initials: L
authors.lastname: Chi
authors.forename: Alevtina
authors.initials: A
authors.lastname: Galtseva
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Mo
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
authors.forename: Norman D
authors.initials: ND
authors.lastname: Rosenblum
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002923:Cilia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016547:Kinesins / Q000172:deficiency / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D009399:Nephrons / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D000074290:Zinc Finger Protein Gli3
chemical_list: C496457:Fgf8 protein, mouse; C465571:Gli3 protein, mouse; C490202:Kif3a protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3; D013629:Tamoxifen; D051524:Fibroblast Growth Factor 8; D016547:Kinesins