Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling

  1. Cathrin Brisken1,
  2. Anna Heineman1,
  3. Tony Chavarria1,
  4. Brian Elenbaas1,
  5. Jian Tan2,
  6. Sudhansu K. Dey2,
  7. Jill A. McMahon3,
  8. Andrew P. McMahon3, and
  9. Robert A. Weinberg1,4
  1. 1Department of Molecular and Integrative Physiology, Whitehead Institute, Cambridge, Massachusetts 02142 USA; 2University of Kansas Medical Center, Kansas City, Kansas 66160 USA; 3Department of Molecular and Cellular Biology, The BioLabs, Harvard University, Cambridge, Massachusetts 02138 USA

Abstract

Female reproductive hormones control mammary gland morphogenesis. In the absence of the progesterone receptor (PR) from the mammary epithelium, ductal side-branching fails to occur. We can overcome this defect by ectopic expression of the protooncogene Wnt-1. Transplantation of mammary epithelia fromWnt-4 / mice shows that Wnt-4 has an essential role in side-branching early in pregnancy. PR andWnt-4 mRNAs colocalize to the luminal compartment of the ductal epithelium. Progesterone induces Wnt-4 in mammary epithelial cells and is required for increased Wnt-4 expression during pregnancy. Thus, Wnt signaling is essential in mediating progesterone function during mammary gland morphogenesis.

Keywords

Footnotes

  • 4 Corresponding author.

  • E-MAIL weinberg{at}mit.edu; FAX (617) 258-5213.

    • Received January 11, 2000.
    • Accepted February 9, 2000.
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