The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis.
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Embargo End Date
ICR Authors
Authors
Soady, KJ
Tornillo, G
Kendrick, H
Meniel, V
Olijnyk-Dallis, D
Morris, JS
Stein, T
Gusterson, BA
Isacke, CM
Smalley, MJ
Tornillo, G
Kendrick, H
Meniel, V
Olijnyk-Dallis, D
Morris, JS
Stein, T
Gusterson, BA
Isacke, CM
Smalley, MJ
Document Type
Journal Article
Date
2017-10-15
Date Accepted
2017-08-25
Abstract
PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here, we demonstrate that PTPRB negatively regulates branching morphogenesis in the mouse mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in oestrogen receptor-positive luminal cells. During mammary development, Ptprb expression is downregulated during puberty, a period of extensive ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of fibroblast growth factor receptor (FGFR) activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology.
Citation
Development (Cambridge, England), 2017, 144 (20), pp. 3777 - 3788
Source Title
Publisher
COMPANY OF BIOLOGISTS LTD
ISSN
0950-1991
eISSN
1477-9129
Collections
Research Team
Molecular Cell Biology