Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation

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dc.contributor.author Georgess, Dan
dc.contributor.author Nguyen-Ngoc, Kim-vy
dc.contributor.author Silvestri, Vanesa
dc.contributor.author Fairchild, Armanda N.
dc.contributor.author Ewald, Andrew J.
dc.date.accessioned 2019-04-04T10:43:44Z
dc.date.available 2019-04-04T10:43:44Z
dc.date.copyright 2017 en_US
dc.date.issued 2019-04-04
dc.identifier.issn 1477-9137 en_US
dc.identifier.uri http://hdl.handle.net/10725/10341
dc.description.abstract The mammary epithelium elaborates through hormonally regulated changes in proliferation, migration and differentiation. Non-muscle myosin II (NMII) functions at the interface between contractility, adhesion and signal transduction. It is therefore a plausible regulator of mammary morphogenesis. We tested the genetic requirement for NMIIA and NMIIB in mammary morphogenesis through deletion of the three NMII heavy chain-encoding genes (NMHCIIA, NMHCIIB and NMHCIIC; also known as MYH9, MYH10 and MYH14, respectively) that confer specificity to the complex. Surprisingly, mosaic loss, but not ubiquitous loss, of NMHCIIA and NMHCIIB induced high levels of proliferation in 3D culture. This phenotype was observed even when cells were cultured in basal medium, which does not support tissue level growth of wild-type epithelium. Mosaic loss of NMIIA and NMIIB combined with FGF signaling to induce hyperplasia. Mosaic analysis revealed that the cells that were null for both NMIIA and NMIIB, as well as wild-type cells, proliferated, indicating that the regulation of proliferation is both cell autonomous and non-autonomous within epithelial tissues. This phenotype appears to be mediated by cell–cell contact, as co-culture did not induce proliferation. Mosaic loss of NMIIA and NMIIB also induced excess proliferation in vivo. Our data therefore reveal a role for NMIIA and NMIIB as negative regulators of proliferation in the mammary epithelium. en_US
dc.language.iso en en_US
dc.title Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201900498 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Journal of Cell Science en_US
dc.journal.volume 2017 en_US
dc.journal.issue 130 en_US
dc.article.pages 3213-3221 en_US
dc.identifier.doi http://dx.doi.org/10.1242/jcs.208546 en_US
dc.identifier.ctation Nguyen-Ngoc, K. V., Silvestri, V. L., Georgess, D., Fairchild, A. N., & Ewald, A. J. (2017). Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation. J Cell Sci, 130(19), 3213-3221. en_US
dc.author.email dan.georgess@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://jcs.biologists.org/content/130/19/3213.abstract en_US
dc.author.affiliation Lebanese American University en_US

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