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

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 (, and; also known as , and , respectively) that confer specificity to the complex. Surprisingly, mosaic loss, but not ubiquitous loss, of and 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 Our data therefore reveal a role for NMIIA and NMIIB as negative regulators of proliferation in the mammary epithelium.

ROCK inhibitor combined with Ca2+ controls the myosin II activation and optimizes human nasal epithelial cell sheets

“…Based on these results, we suggest that P-MLC at the cell periphery prevents cell proliferation (Fig. 2D,G), consistent with a previous report that cell proliferation is induced by the mosaic loss of myosin and 50-75% of MLC 11 . The purpose of cell sheet culture is to connect cells to each other so that all the cells can be detached as an intact construct.…”

“…Based on these results, we suggest that P-MLC at the cell periphery prevents cell proliferation (Fig. 2 D,G), consistent with a previous report that cell proliferation is induced by the mosaic loss of myosin and 50–75% of MLC 11 .…”

Keratin 6 regulates collective keratinocyte migration by altering cell–cell and cell–matrix adhesion

“…Krt6a/Krt6b hemizygous null mice (Wong et al, 2000) are viable and were maintained in the inbred C57Bl/6 background (Rotty and Coulombe, 2012). K14-GFP-actin mice (Vaezi et al, 2002), Dsp fl/fl mice (Vasioukhin et al, 2001), and Myh9 fl/fl mice (Ma et al, 2009; Jacobelli et al, 2010; Nguyen-Ngoc et al, 2017) were gifts from A. Ewald (Johns Hopkins University, Baltimore, MD).…”

Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

“…It also has angiogenesis, vascular remodeling abilities in vascular endothelial cells [66] and promotes tumor invasion, metastasis in some tumors [64,67]. Furthermore, Myh9 promotes tumor invasion and metastasis in some tumors [65,[68][69][70]. In addition, some studies have shown that Myh9 also contributes to cell proliferation, cell contraction, adhesion and cytokinesis.…”