ID4 regulates mammary gland development by suppressing p38MAPK activity

Development. 2011 Dec;138(23):5247-56. doi: 10.1242/dev.069203.


The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bromodeoxyuridine
  • Cell Proliferation / drug effects
  • Estradiol / pharmacology
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Immunoblotting
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inhibitor of Differentiation Proteins / genetics*
  • Inhibitor of Differentiation Proteins / metabolism*
  • Mammary Glands, Animal / growth & development*
  • Mammary Glands, Animal / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Progesterone / pharmacology
  • Real-Time Polymerase Chain Reaction
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Idb4 protein, mouse
  • Inhibitor of Differentiation Proteins
  • Progesterone
  • Estradiol
  • p38 Mitogen-Activated Protein Kinases
  • Bromodeoxyuridine