Barrett A L, Krueger S, Datta S
Department of Biochemistry and Biophysics, MS 2128, Texas A&M University, College Station, TX 77843-2128, USA.
Dev Biol. 2008 May 1;317(1):234-45. doi: 10.1016/j.ydbio.2008.02.025. Epub 2008 Mar 4.
The Drosophila central nervous system is produced by two rounds of neurogenesis: one during embryogenesis to form the larval brain and one during larval stages to form the adult central nervous system. Neurogenesis caused by the activation of neural stem division in the larval brain is essential for the proper patterning and functionality of the adult central nervous system. Initiation of neuroblast proliferation requires signaling by the Fibroblast Growth Factor homolog Branchless and by the Hedgehog growth factor. We show here that the Branchless and Hedgehog pathways form a positive feedback loop to regulate the onset of neuroblast division. This feedback loop is initiated during embryogenesis. Our genetic and molecular studies demonstrate that the absolute level of Branchless and Hedgehog signaling is critical to fully activate stem cell division. Furthermore, over-expression and mutant studies establish that signaling by Branchless is the crucial output of the feedback loop that stimulates neuroblast division and that Branchless signaling is necessary for initiating the division of all mitotically regulated neuroblasts in the brain lobes. These studies establish the molecular mechanism through which Branchless and Hedgehog signaling interface to regulate the activation of neural stem cell division.
一轮在胚胎发育期间形成幼虫脑，另一轮在幼虫阶段形成成体中枢神经系统。幼虫脑中神经干细胞分裂激活所引发的神经发生对于成体中枢神经系统的正常模式形成和功能至关重要。神经母细胞增殖的起始需要成纤维细胞生长因子同源物“无分支”（Branchless）和刺猬索尼克因子（Hedgehog）的信号传导。我们在此表明，“无分支”和刺猬索尼克因子信号通路形成一个正反馈环来调节神经母细胞分裂的起始。这个反馈环在胚胎发育期间启动。我们的遗传学和分子研究表明，“无分支”和刺猬索尼克因子信号的绝对水平对于完全激活干细胞分裂至关重要。此外，过表达和突变研究证实，“无分支”信号传导是刺激神经母细胞分裂的反馈环的关键输出，并且“无分支”信号传导对于启动脑叶中所有有丝分裂调控的神经母细胞的分裂是必需的。这些研究确立了“无分支”和刺猬索尼克因子信号相互作用以调节神经干细胞分裂激活的分子机制。
