Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Development. 2010 Oct;137(19):3193-203. doi: 10.1242/dev.048058. Epub 2010 Aug 19.
During neurogenesis in the medulla of the Drosophila optic lobe, neuroepithelial cells are programmed to differentiate into neuroblasts at the medial edge of the developing optic lobe. The wave of differentiation progresses synchronously in a row of cells from medial to the lateral regions of the optic lobe, sweeping across the entire neuroepithelial sheet; it is preceded by the transient expression of the proneural gene lethal of scute [l(1)sc] and is thus called the proneural wave. We found that the epidermal growth factor receptor (EGFR) signaling pathway promotes proneural wave progression. EGFR signaling is activated in neuroepithelial cells and induces l(1)sc expression. EGFR activation is regulated by transient expression of Rhomboid (Rho), which is required for the maturation of the EGF ligand Spitz. Rho expression is also regulated by the EGFR signal. The transient and spatially restricted expression of Rho generates sequential activation of EGFR signaling and assures the directional progression of the differentiation wave. This study also provides new insights into the role of Notch signaling. Expression of the Notch ligand Delta is induced by EGFR, and Notch signaling prolongs the proneural state. Notch signaling activity is downregulated by its own feedback mechanism that permits cells at proneural states to subsequently develop into neuroblasts. Thus, coordinated sequential action of the EGFR and Notch signaling pathways causes the proneural wave to progress and induce neuroblast formation in a precisely ordered manner.
在果蝇视神经叶的髓质中发生神经发生时，神经上皮细胞被编程在发育中的视神经叶的内侧边缘分化为神经母细胞。分化波从视神经叶的内侧到外侧区域的一排细胞中同步进行，横扫整个神经上皮层；它之前是瞬时表达神经前基因 lethal of scute [l(1)sc]，因此称为神经前波。我们发现表皮生长因子受体 (EGFR) 信号通路促进了神经前波的进展。EGFR 信号在神经上皮细胞中被激活，并诱导 l(1)sc 表达。EGFR 激活受 Rhomboid (Rho) 的瞬时表达调节，Rho 对于 EGF 配体 Spitz 的成熟是必需的。Rho 的表达也受 EGFR 信号的调节。Rho 的瞬时和空间限制表达产生 EGFR 信号的顺序激活，并确保分化波的定向进展。这项研究还为 Notch 信号的作用提供了新的见解。Notch 配体 Delta 的表达受 EGFR 诱导，并且 Notch 信号延长了神经前状态。Notch 信号活性通过其自身的反馈机制下调，该机制允许处于神经前状态的细胞随后发育成神经母细胞。因此，EGFR 和 Notch 信号通路的协调顺序作用导致神经前波的进展，并以精确有序的方式诱导神经母细胞的形成。
