TGF-beta signals regulate axonal development through distinct Smad-independent mechanisms.
Proper nerve connections form when growing axons terminate at the correct postsynaptic target. Here I show that Transforming growth factor beta (TGFbeta) signals regulate axon growth. In most contexts, TGFbeta signals are tightly linked to Smad transcriptional activity. Although known to exist, how Smad-independent pathways mediate TGFbeta responses in vivo is unclear. In Drosophila mushroom body (MB) neurons, loss of the TGFbeta receptor Baboon (Babo) results in axon overextension. Conversely, misexpression of constitutively active Babo results in premature axon termination. Smad activity is not required for these phenotypes. This study shows that Babo signals require the Rho GTPases Rho1 and Rac, and LIM kinase1 (LIMK1), which regulate the actin cytoskeleton. Contrary to the well-established receptor activation model, in which type 1 receptors act downstream of type 2 receptors, this study shows that the type 2 receptors Wishful thinking (Wit) and Punt act downstream of the Babo type 1 receptor. Wit and Punt regulate axon growth independently, and interchangeably, through LIMK1-dependent and -independent mechanisms. Thus, novel TGFbeta receptor interactions control non-Smad signals and regulate multiple aspects of axonal development in vivo.
Ng
Julian
J
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, SE1 1UL, UK. julian.ng@kcl.ac.uk
D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000502:physiology; D029404:Activin Receptors / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D017344:Genes, Insect; D054461:Lim Kinases / Q000235:genetics / Q000502:physiology; D008959:Models, Neurological; D024521:Mushroom Bodies / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology
D051339:Actin Depolymerizing Factors; D029721:Drosophila Proteins; D011956:Receptors, Cell Surface; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C449821:wit protein, Drosophila; C515892:LIMK1 protein, human; D054461:Lim Kinases; D029404:Activin Receptors; C517157:Babo protein, Drosophila; C511153:Rho1 protein, Drosophila; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins