ECM-modulated cellular dynamics as a driving force for tissue morphogenesis

Abstract

The extracellular matrix (ECM) plays diverse regulatory roles throughout development. Coordinate interactions between cells within a tissue and the ECM result in the dynamic remodeling of ECM structure. Both chemical signals and physical forces that result from such microenvironmental remodeling regulate cell behavior that sculpts tissue structure. Here, we review recent discoveries illustrating different ways in which ECM remodeling promotes dynamic cell behavior during tissue morphogenesis. We focus first on new insights that identify localized ECM signaling as a regulator of cell migration, shape, and adhesion during branching morphogenesis. We also review mechanisms by which the ECM and basement membrane can both sculpt and stabilize epithelial tissue structure, using as examples Drosophila egg chamber development and cleft formation in epithelial organs. Finally, we end with an overview of the dynamic mechanisms by which the ECM can regulate stem cell differentiation to contribute to proper tissue morphogenesis.

RETRACTED: Btbd7 is essential for region-specific epithelial cell dynamics and branching morphogenesis in vivo

“…These novel findings establish that Btbd7 can locally govern epithelial cell dynamics specifically within the outer tip cells during branching morphogenesis. Collective cell migration has been implicated as a cellular mechanism that drives branching morphogenesis (Daley and Yamada, 2013;Ewald et al, 2008;Friedl and Gilmour, 2009). Some branching systems, including Drosophila trachea and angiogenic sprouting, initiate new branches through a form of invasive collective cell migration in which protrusive tip cells extend filopodia into the surrounding ECM (Ochoa-Espinosa and Affolter, 2012).…”

“…Although many studies have highlighted requirements for numerous signaling molecules and transcription factors during branching morphogenesis (Costantini and Kopan, 2010;Harunaga et al, 2011;Hauser and Hoffman, 2015;Hennighausen and Robinson, 2005;Iber and Menshykau, 2013;Kwon and Larsen, 2015;Shih et al, 2013;Varner and Nelson, 2014), it is not fully understood at the cell and tissue level how such diverse regulatory pathways orchestrate the extensive physical remodeling that shapes branched epithelial tissues. Recent advances in microscopy have established that specific dynamic cell behaviors, such as changes in cell motility, cell-cell adhesion and cell-extracellular matrix interactions, are key functional mediators of this tissue reorganization (Daley and Yamada, 2013;Friedl and Gilmour, 2009;Harunaga et al, 2011;Huebner and Ewald, 2014;Kim and Nelson, 2012;Nelson and Larsen, 2015;Varner and Nelson, 2014). However, how such dynamic cell and tissue behavior is guided by localized regulatory molecules at specific sites within a tissue remains largely unknown.…”

FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands

“…Components of the ECM, including collagens, laminins, glycoproteins and proteoglycans, are essential for branching morphogenesis Pritchett et al, 2011;Kim and Nelson, 2012;Daley and Yamada, 2013). Sox9 has been reported to regulate several genes encoding ECM components (Pritchett et al, 2011).…”

An active role for basement membrane assembly and modification in tissue sculpting

“…morphogenesis (Daley and Yamada, 2013;Onodera et al, 2010;Sakai et al, 2003). Fibronectin induces the expression of the transcription factor Snail2 and suppresses E-cadherin, leading to cell separation at the cleft (Onodera et al, 2010).…”