Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development

John Foley, P. Dann, J. Hong, J. Cosgrove, B. Dreyer, D. Rimm, M. E. Dunbar, W. Philbrick, J. J. Wysolmerski

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and β-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways.

Original languageEnglish (US)
Pages (from-to)513-525
Number of pages13
JournalDevelopment (Cambridge)
Volume128
Issue number4
StatePublished - 2001
Externally publishedYes

Fingerprint

Parathyroid Hormone-Related Protein
Nipples
Embryonic Development
Breast
Skin
Epithelial Cells
Mesoderm
Morphogenesis
Epidermis
Catenins
Wnt Signaling Pathway
Human Mammary Glands
Dermis
Epithelium
Maintenance

Keywords

  • Epithelial-mesenchymal interactions
  • Keratinocyte differentiation
  • Mammary development
  • Mouse
  • Nipple
  • PTH/PTHrP receptor
  • PTHrP

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. / Foley, John; Dann, P.; Hong, J.; Cosgrove, J.; Dreyer, B.; Rimm, D.; Dunbar, M. E.; Philbrick, W.; Wysolmerski, J. J.

In: Development (Cambridge), Vol. 128, No. 4, 2001, p. 513-525.

Research output: Contribution to journalArticle

Foley, J, Dann, P, Hong, J, Cosgrove, J, Dreyer, B, Rimm, D, Dunbar, ME, Philbrick, W & Wysolmerski, JJ 2001, 'Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development', Development (Cambridge), vol. 128, no. 4, pp. 513-525.
Foley, John ; Dann, P. ; Hong, J. ; Cosgrove, J. ; Dreyer, B. ; Rimm, D. ; Dunbar, M. E. ; Philbrick, W. ; Wysolmerski, J. J. / Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. In: Development (Cambridge). 2001 ; Vol. 128, No. 4. pp. 513-525.
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