title: Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney.
abstract: The developing mammalian kidney is an attractive system in which to study the control of organ growth. Targeted mutations in the Wnt receptors frizzled (Fz) 4 and Fz8 lead to reduced ureteric bud growth and a reduction in kidney size, a phenotype previously reported for loss of Wnt11. In cell culture, Fz4 and Fz8 can mediate noncanonical signaling stimulated by Wnt11, but only Fz4 mediates Wnt11-stimulated canonical signaling. In genetically mosaic mouse ureteric buds, competition between phenotypically mutant Fz4(-/-) or Fz4(-/-);Fz8(-/-) cells and adjacent phenotypically wild-type Fz4(+/-) or Fz4(+/-);Fz8(-/-) cells results in under-representation of the mutant cells to an extent far greater than would be predicted from the size reduction of homogeneously mutant kidneys. This discrepancy presumably reflects the compensatory action of a network of growth regulatory systems that minimize developmental perturbations. The present work represents the first description of a kidney phenotype referable to one or more Wnt receptors and demonstrates a general strategy for revealing the contribution of an individual growth regulatory pathway when it is part of a larger homeostatic network.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Wang
authors.forename: Amir
authors.initials: A
authors.lastname: Rattner
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D007668:Kidney / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009030:Mosaicism / Q000196:embryology; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014513:Ureter / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism
chemical_list: D051157:Frizzled Receptors; D043562:Receptors, G-Protein-Coupled; C498581:Fzd4 protein, mouse; C511610:Fzd8 protein, mouse