Stromal Hoxa5 function controls the growth and differentiation of mammary alveolar epithelium
Version of Record online: 10 APR 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 235, Issue 7, pages 1858–1871, July 2006
How to Cite
Garin, É., Lemieux, M., Coulombe, Y., Robinson, G. W. and Jeannotte, L. (2006), Stromal Hoxa5 function controls the growth and differentiation of mammary alveolar epithelium. Dev. Dyn., 235: 1858–1871. doi: 10.1002/dvdy.20822
- Issue online: 22 MAY 2006
- Version of Record online: 10 APR 2006
- Manuscript Accepted: 14 MAR 2006
- Cancer Research Society
- Fonds de la Recherche en Santé du Québec
- Hox genes;
- mammary gland development;
Recent progress has enlightened the involvement of Hox genes in organogenesis. Several Hox genes are expressed in normal and neoplastic mammary glands. Using Hoxa5 mutant mice, we showed that Hoxa5−/− females present nursing defects. Characterization of the Hoxa5−/− mammary gland phenotype reveals changes in proliferation and differentiation of the epithelium of nulliparous and pregnant Hoxa5−/− females that precede the abnormal secretory activity at parturition. These defects likely underlie the incapacity of Hoxa5−/− dams to properly feed their pups. Hoxa5 expression is restricted to the mammary stroma at specific stages of mammary gland development. The loss of Hoxa5 function causes accelerated lobuloalveolar epithelium development, a phenotype that can be rescued upon grafting of mutant mammary epithelium into wild-type fat pads. Conversely, reciprocal grafting experiments demonstrate that Hoxa5−/− stroma cannot support normal proliferation of wild-type mammary epithelium. These data establish the essential contribution of Hoxa5 to mammary epithelium instruction by means of mesenchymal–epithelial crosstalk. Developmental Dynamics 235:1858–1871, 2006. © 2006 Wiley-Liss, Inc.