Zhu Changqi C, Boone Jason Q, Jensen Philip A, Hanna Scott, Podemski Lynn, Locke John, Doe Chris Q, O'Connor Michael B
Department of Genetics, Cell Biology and Development, Howard Hughes Medical Institute, University of Minnesota, 6-160 Jackson Hall, Minneapolis, MN 55455, USA.
Development. 2008 Feb;135(3):513-21. doi: 10.1242/dev.010876. Epub 2008 Jan 2.
The Drosophila Activin-like ligands Activin-beta and Dawdle control several aspects of neuronal morphogenesis, including mushroom body remodeling, dorsal neuron morphogenesis and motoneuron axon guidance. Here we show that the same two ligands act redundantly through the Activin receptor Babo and its transcriptional mediator Smad2 (Smox), to regulate neuroblast numbers and proliferation rates in the developing larval brain. Blocking this pathway results in the development of larvae with small brains and aberrant photoreceptor axon targeting, and restoring babo function in neuroblasts rescued these mutant phenotypes. These results suggest that the Activin signaling pathway is required for producing the proper number of neurons to enable normal connection of incoming photoreceptor axons to their targets. Furthermore, as the Activin pathway plays a key role in regulating propagation of mouse and human embryonic stem cells, our observation that it also regulates neuroblast numbers and proliferation in Drosophila suggests that involvement of Activins in controlling stem cell propagation may be a common regulatory feature of this family of TGF-beta-type ligands.
果蝇激活素样配体激活素-β和达德尔控制神经元形态发生的多个方面，包括蘑菇体重塑、背侧神经元形态发生和运动神经元轴突导向。我们在此表明，这两种配体通过激活素受体巴波及其转录介质Smad2（Smox）发挥冗余作用，以调节发育中幼虫大脑中的神经母细胞数量和增殖速率。阻断该信号通路会导致幼虫发育出小的大脑和异常的光感受器轴突靶向，而在神经母细胞中恢复巴波功能可挽救这些突变表型。这些结果表明，激活素信号通路对于产生适当数量的神经元以实现传入光感受器轴突与其靶标的正常连接是必需的。此外，由于激活素信号通路在调节小鼠和人类胚胎干细胞的增殖中起关键作用，我们观察到它也调节果蝇中的神经母细胞数量和增殖，这表明激活素参与控制干细胞增殖可能是该TGF-β型配体家族的一个共同调节特征。
