Ng Julian
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, SE1 1UL, UK.
Development. 2008 Dec;135(24):4025-35. doi: 10.1242/dev.028209. Epub 2008 Nov 12.
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.
当生长中的轴突在正确的突触后靶点终止时,会形成适当的神经连接。在此我表明,转化生长因子β(TGFβ)信号调节轴突生长。在大多数情况下,TGFβ信号与Smad转录活性紧密相连。虽然已知存在,但Smad非依赖途径如何在体内介导TGFβ反应尚不清楚。在果蝇蘑菇体(MB)神经元中,TGFβ受体狒狒(Babo)缺失会导致轴突过度延伸。相反,组成型活性Babo的错误表达会导致轴突过早终止。这些表型不需要Smad活性。本研究表明,Babo信号需要Rho GTP酶Rho1和Rac以及调节肌动蛋白细胞骨架的LIM激酶1(LIMK1)。与已确立的1型受体在2型受体下游起作用的受体激活模型相反,本研究表明,2型受体如意算盘(Wit)和蓬特(Punt)在Babo 1型受体下游起作用。Wit和Punt通过LIMK1依赖和非依赖机制独立且可互换地调节轴突生长。因此,新型TGFβ受体相互作用控制非Smad信号并在体内调节轴突发育的多个方面。