Skip to main content
Article
Analysis of Gene Expression in PTHrP−/− Mammary Buds Supports a Role for BMP Signaling and MMP2 in the Initiation of Ductal Morphogenesis
Developmental Dynamics (2009)
  • Julie Hens
  • Pamela Dann
  • Minoti Hiremath
  • Tien-Chi Pan
  • Lewis Chodosh
  • John Wysolmerski
Abstract

Parathyroid hormone–related protein (PTHrP) acts on the mammary mesenchyme and is required for proper embryonic mammary development. In order to understand PTHrP's effects on mesenchymal cells, we profiled gene expression in WT and PTHrP−/− mammary buds, and in WT and K14-PTHrP ventral skin at E15.5. By cross-referencing the differences in gene expression between these groups, we identified 35 genes potentially regulated by PTHrP in the mammary mesenchyme, including 6 genes known to be involved in BMP signaling. One of these genes was MMP2. We demonstrated that PTHrP and BMP4 regulate MMP2 gene expression and MMP2 activity in mesenchymal cells. Using mammary bud cultures, we demonstrated that MMP2 acts downstream of PTHrP to stimulate ductal outgrowth. Future studies on the functional role of other genes on this list should expand our knowledge of how PTHrP signaling triggers the onset of ductal outgrowth from the embryonic mammary buds.

Keywords
  • parathyroid hormone–related protein,
  • mammary development,
  • ductal morphogenesis,
  • oligonucleotide gene arrays,
  • matrix metalloproteinase,
  • epidermal appendage
Publication Date
November, 2009
Citation Information
Julie Hens, Pamela Dann, Minoti Hiremath, Tien-Chi Pan, et al.. "Analysis of Gene Expression in PTHrP−/− Mammary Buds Supports a Role for BMP Signaling and MMP2 in the Initiation of Ductal Morphogenesis" Developmental Dynamics Vol. 238 Iss. 11 (2009)
Available at: http://works.bepress.com/minoti_hiremath/5/