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The Rho small GTPases regulate a variety of cellular functions, including proliferation, differentiation, vesicle trafficking, gene expression, adhesion, and motility. Among their well established essential roles is that of organizing the actin cytoskeleton, and this aspect of Rho GTPase function has led to the identification of important roles for various Rho family GTPases in a variety of actin-dependent cellular processes, including cell shape change, adhesion, and migration. As critical regulators of these actin-mediated processes, the Rho GTPases also function as essential regulators of many developmental processes. The morphogenesis of tissues in all developing multi-cellular organisms requires precise changes in cell shape and cell movements that depend on the various Rho GTPases. This has been observed in studies using sevefigureral different developmental model systems, including flies, worms, frogs, and mice. Here, we review the literature reporting functions for Rho GTPases and their associated signaling components in the context of embryonic development, adult physiology, and pathogenesis. In particular, the focus of the studies described here is on the mouse system, where transgenic and “knockout” strategies have played an especially important role in elucidating the in vivo organization and function of the various Rho signaling pathways.

Rho GTPases have increasingly become recognized as prominent regulators of the microtubule (MT) cytoskeleton. Whereas Rho GTPases regulate the de novo formation of distinct actin arrays (stress fibers, lamellipodia, and filopodia), with MTs, which are present as extensive and dynamic arrays in the absence of Rho GTPase signaling, Rho GTPases principally modify the behavior and dynamics of individual MTs within an existing array. Despite this seemingly modulatory role, Rho GTPases have to profound effects on the MT cytoskeleton. The action of Rho GTPases is primarily exerted at the ends of MTs and causes changes in: (1) dynamics of MT plus ends either through MAPs or sequestering proteins, (2) interactions of MT plus ends with targets in the cortex, in kinetochores or at other sites, a process termed MT capture or (3) the activity of MT minus ends at the centrosome. In many cases, specific GTPases and effectors are known to regulate each of these processes and constitute signaling pathways to regulate MTs. Additionally, MTs can in turn influence the activity of Rho GTPases by interacting with the guanine exchange factors (GEFs) and GTPase activating proteins (GAPs) regulating their function. Together, MTs and Rho GTPases have a dynamic relationship that allows a cell to quickly respond to and integrate a variety of stimuli.