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Publication : Basal cell signaling by p63 controls luminal progenitor function and lactation via NRG1.

First Author  Forster N Year  2014
Journal  Dev Cell Volume  28
Issue  2 Pages  147-60
PubMed ID  24412575 Mgi Jnum  J:208347
Mgi Id  MGI:5562960 Doi  10.1016/j.devcel.2013.11.019
Citation  Forster N, et al. (2014) Basal cell signaling by p63 controls luminal progenitor function and lactation via NRG1. Dev Cell 28(2):147-60
abstractText  The mammary epithelium is organized as a bilayer of luminal and basal/myoepithelial cells. During pregnancy, the luminal compartment expands for milk production, while basal cells are thought to provide structural and contractile support. Here, we reveal a pregnancy-specific role of basal epithelia as a central coordinator of lactogenesis. We demonstrate that genetic deletion of the transcription factor p63 (Trp63) gene exclusively within basal cells of the adult gland during pregnancy leads to dramatic defects in luminal cell proliferation and differentiation, resulting in lactation failure. This phenotype is explained by direct transcriptional activation of the epidermal growth factor family ligand gene Nrg1 by p63 selectively in basal cells, which is required for luminal ERBB4/STAT5A activation and consequent luminal progenitor cell maturation. Thus, paracrine basal-to-luminal cell signaling, controlled by p63 via NRG1, orchestrates the entire lactation program. Collectively, these findings redefine the paradigm for cellular interactions specifying the functional maturation of the mammary gland.
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