Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney

Development. 2011 Mar;138(6):1161-72. doi: 10.1242/dev.057620.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Frizzled Receptors / physiology*
  • Gene Expression Regulation, Developmental
  • Gene Transfer Techniques
  • Kidney / embryology*
  • Kidney / growth & development
  • Kidney / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mosaicism* / embryology
  • Pregnancy
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • Ureter / embryology*
  • Ureter / growth & development
  • Ureter / metabolism

Substances

  • Frizzled Receptors
  • Fzd4 protein, mouse
  • Receptors, G-Protein-Coupled
  • frizzled 8 protein, mouse