Yasugi Tetsuo, Umetsu Daiki, Murakami Satoshi, Sato Makoto, Tabata Tetsuya
Laboratory of Pattern Formation, Institute of Molecular and Cellular Biosciences, the University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
Development. 2008 Apr;135(8):1471-80. doi: 10.1242/dev.019117. Epub 2008 Mar 13.
Neural stem cells called neuroblasts (NBs) generate a variety of neuronal and glial cells in the central nervous system of the Drosophila embryo. These NBs, few in number, are selected from a field of neuroepithelial (NE) cells. In the optic lobe of the third instar larva, all NE cells of the outer optic anlage (OOA) develop into either NBs that generate the medulla neurons or lamina neuron precursors of the adult visual system. The number of lamina and medulla neurons must be precisely regulated because photoreceptor neurons project their axons directly to corresponding lamina or medulla neurons. Here, we show that expression of the proneural protein Lethal of scute [L(1)sc] signals the transition of NE cells to NBs in the OOA. L(1)sc expression is transient, progressing in a synchronized and ordered ;proneural wave' that sweeps toward more lateral NEs. l(1)sc expression is sufficient to induce NBs and is necessary for timely onset of NB differentiation. Thus, proneural wave precedes and induces transition of NE cells to NBs. Unpaired (Upd), the ligand for the JAK/STAT signaling pathway, is expressed in the most lateral NE cells. JAK/STAT signaling negatively regulates proneural wave progression and controls the number of NBs in the optic lobe. Our findings suggest that NBs might be balanced with the number of lamina neurons by JAK/STAT regulation of proneural wave progression, thereby providing the developmental basis for the formation of a precise topographic map in the visual center.
被称为神经母细胞（NBs）的神经干细胞在果蝇胚胎的中枢神经系统中产生多种神经元和神经胶质细胞。这些数量稀少的神经母细胞是从神经上皮（NE）细胞群中挑选出来的。在三龄幼虫的视叶中，外视神经原基（OOA）的所有神经上皮细胞都会发育成产生髓质神经元的神经母细胞或成年视觉系统的层神经元前体。由于光感受器神经元将其轴突直接投射到相应的层或髓质神经元，因此层和髓质神经元的数量必须得到精确调节。在这里，我们表明，原神经蛋白“scute致死”[L(1)sc]的表达标志着神经上皮细胞在OOA中向神经母细胞的转变。L(1)sc的表达是短暂的，以同步且有序的“原神经波”形式推进，该波朝着更外侧的神经上皮细胞扫去。L(1)sc的表达足以诱导神经母细胞的产生，并且对于神经母细胞分化的及时开始是必需的。因此，原神经波先于并诱导神经上皮细胞向神经母细胞的转变。JAK/STAT信号通路的配体“未配对”（Upd）在最外侧的神经上皮细胞中表达。JAK/STAT信号负向调节原神经波的推进，并控制视叶中神经母细胞的数量。我们的研究结果表明，神经母细胞的数量可能通过JAK/STAT对原神经波推进的调节与层神经元的数量达到平衡，从而为视觉中枢精确地形图的形成提供发育基础。
