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Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis
Author(s) -
Zhang Yue,
Li Fengyin,
Song Yongli,
Sheng Xiaole,
Ren Fazheng,
Xiong Kai,
Chen Lei,
Zhang Hongquan,
Liu Dequan,
Lengner Christopher J.,
Xue Lixiang,
Yu Zhengquan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600387r
Subject(s) - myoepithelial cell , numb , biology , mammary gland , epithelium , lactation , microbiology and biotechnology , medicine , endocrinology , immunology , cancer , immunohistochemistry , pregnancy , breast cancer , genetics
Mammary epithelium is comprised of an inner layer of luminal epithelial cells and an outer layer of contractile myoepithelial cells with mesenchymal properties. These two compartments interact throughout mammary morphogenesis to form branching ducts during puberty and terminate in secretory alveoli during lactation. It is not known how the myoepithelial cell lineage is specified, nor how signals in myoepithelial cells contribute to lactogenesis. Here, we show that Numb and Numbl are enriched in mammary myoepithelial cells, with their expression peaking during pregnancy. We use conditional Numb ‐and Numbl‐knockout mouse models to demonstrate that loss of Numb / Numbl compromised the myoepithelial layer and expanded the luminal layer, led epithelial cells to undergo epithelial‐to‐mesenchymal transition, and resulted in lactation failure as a result of abnormal alveolar formation during pregnancy. Numb and Numbl function via repression of the Notch signaling pathway and of the p53–p21 axis during mammary gland development. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis.—Zhang Y., Li, F., Song, Y., Sheng, X., Ren, F., Xiong, K., Chen, L., Zhang, H., Liu, D., Lengner, C. J., Xue, L., Yu, Z. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis. FASEB J. 30, 3474–3488 (2016). www.fasebj.org