Settleman J
Massachusetts General Hospital Cancer Center, Charlestown, USA.
Prog Mol Subcell Biol. 1999;22:201-29. doi: 10.1007/978-3-642-58591-3_10.
It is becoming increasingly clear that the complex family of Rho-related GTPases and their associated regulators and targets are essential mediators of a variety of morphogenetic events required for normal development of multicellular organisms. It is worth noting that the results obtained thus far indicate that the Rho family proteins are largely associated with the regulation of morphogenesis, as opposed to other essential developmental processes such as cell proliferation and cell fate determination. Accumulating evidence also suggests that the role of these proteins and their associated signaling pathways in morphogenesis is in many, but not necessarily all, cases related to their ability to affect the organization of the actin cytoskeleton. Thus, these in vivo observations have served to corroborate similar findings in numerous cultured cell studies. As described, the power of genetics, particularly in Drosophila and C. elegans, has been critical to the recent identification and functional characterization of several Rho family signaling components. Moreover, evidence suggests that the highly evolutionarily conserved structures of many of these proteins translate into conservation of function as well. Thus, it will be possible, in many cases, to extrapolate the findings in the simple systems described herein to higher eukaryotes, including humans. Expanding use of these genetic model systems to dissect Rho-mediated signaling pathways in vivo will undoubtedly lead to a flood of new insights into the organization and function of these pathways in the coming years, especially in development. As the C. elegans genome sequencing effort nears completion and with the Drosophila genome project well underway, the identification of novel relevant genes will proceed with even greater speed. In addition, the rapidly expanding use of mouse knockout strategies, combined with recent developments in the associated knockout technology, will also contribute greatly to the investigation of mammalain Rho signaling pathways and their roles in development.
