Role of Rho family GTPases in epithelial morphogenesis

Epithelial cell sheets line the organ and body surfaces and the specialized barrier functions of these epithelia regulate the exchange of substances with the outside environment and between different body compartments. Epithelia play a role in a wide range of physiological processes such as digestion, excretion, and leukocyte trafficking. In addition, during development, some epithelia form transient primitive structures, including the neural tube and somites, which are essential for the development of more complex organs.

The establishment and maintenance of epithelial cell polarity is critical for the development and functioning of multicellular organisms (Nelson 2000). A multi-step model for the establishment of cell polarity has been proposed by Drubin and Nelson (1996). Cell polarity is initiated by a spatial cue, such as generated by cell–cell contact sites. This cue is interpreted and marked by the formation of signaling complexes that relay the spatial information to the actin cytoskeleton. Localized actin assembly then leads to the formation of a targeting patch, which functions to reinforce the initial cue. Subsequently, this cue can further be propagated via a reorganization of the microtubule cytoskeleton, which in turn causes a redistribution of the membrane trafficking apparatus.

In addition to actin cytoskeletal dynamics and vesicle trafficking, epithelial morphogenesis also depends on cell–substrate and cell–cell adhesion. Members of the Rho family of GTPases play essential roles in each of these processes (for reviews, see Hall 1998; Kaibuchi et al. 1999a,b; Braga 2000; Ellis and Mellor 2000; Schwartz and Shattil 2000;Ridley 2001a,b) and therefore it is not surprising to see that Rho GTPases have emerged as critical players at multiple stages of epithelial morphogenesis. In this review we will discuss the involvement of Rho family members in the development and maintenance of epithelial morphology and highlight …