Semaphorins are secreted signals that function during diverse developmental events, from axon guidance to angiogenesis. Although the plexin A family of semaphorin receptors has been well characterised, less is known about the B-type plexins, particularly their roles in organogenesis. Now Korostylev et al. have discovered that the Sema4d-plexin B1 ligand-receptor pair negatively regulates branching morphogenesis during kidney development by RhoA-ROCK pathway activation (see ). By analysing the expression of this pair in developing organs,the authors found that plexin B1 and Sema4d are expressed in epithelial and mesenchymal compartments, respectively, implicating them in the epithelial-mesenchymal interactions that occur during organogenesis. Next, in cultured mouse embryonic kidneys, they found that exogenously applied Sema4d reduces ureteric branching and activates RhoA. However, when they blocked the RhoA-ROCK pathway, Sema4d stimulated ureteric branching. From these findings,the authors conclude that RhoA-ROCK signalling acts as an endogenous brake on plexin B1-triggered, branch-promoting signalling through a function that is distinct from ROCK's maintenance of the cytoskeletal structure of the ureteric tree.
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