Conditional Knockout of Fibronectin Abrogates Mouse Mammary Gland Lobuloalveolar Differentiation

Dev Biol. 2010 Oct 1;346(1):11-24. doi: 10.1016/j.ydbio.2010.07.001. Epub 2010 Aug 10.

Abstract

Fibronectin (Fn) plays an important part in the branching morphogenesis of salivary gland, lung, and kidney. Here, we examine the effect of the conditional knockout of Fn in the mammary epithelium [Fn(MEp-/-)] on postnatal mammary gland development, using Cre-loxP-mediated gene knockout technology. Our data show that Fn deletion causes a moderate retardation in outgrowth and branching of the ductal tree in 5-week-old mice. These defects are partially compensated in virgin 16-week-old mice. However, mammary glands consisting of Fn-deficient epithelial cells fail to undergo normal lobuloalveolar differentiation during pregnancy. The severity of lobuloalveolar impairment ranged from lobular hypoplasia to aplasia in some cases and was associated with the amount of Fn protein recovered from these glands. Decreased rates of mammary epithelial cell proliferation accounted for delayed ductal outgrowth in virgin and lack of alveologenesis in pregnant Fn(MEp-/-) mice. Concomitant decreased expression of integrin beta(1) (Itgb1) and lack of autophosphorylation of focal adhesion kinase (Fak) suggest that this pathology might, at least in part, be mediated by disruption of the Fn/Itgb1/Fak signaling pathway.

Publication types

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

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation
  • Female
  • Fibronectins / physiology*
  • Focal Adhesion Protein-Tyrosine Kinases / physiology
  • Hyperplasia
  • Integrases / physiology
  • Integrin beta1 / physiology
  • Keratin-8 / analysis
  • Mammary Glands, Animal / blood supply
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / growth & development*
  • Mammary Glands, Animal / pathology
  • Mammary Tumor Virus, Mouse / genetics
  • Mice
  • Morphogenesis
  • Neovascularization, Physiologic
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Pregnancy
  • Recombination, Genetic

Substances

  • Fibronectins
  • Integrin beta1
  • Keratin-8
  • Krt8 protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Cre recombinase
  • Integrases
  • Bromodeoxyuridine