Coordinated sequential action of EGFR and Notch signaling pathways regulates proneural wave progression in the Drosophila optic lobe
Coordinated sequential action of EGFR and Notch signaling pathways regulates proneural wave progression in the Drosophila optic lobe
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DOI：
10.1242/dev.048058
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发表时间：
2010-10-01
期刊：
影响因子：
4.6
通讯作者：
Tabata, Tetsuya
中科院分区：
文献类型：
--
作者：
Yasugi, Tetsuo;Sugie, Atsushi;Tabata, Tetsuya
在果蝇视叶髓质的神经发生过程中，神经上皮细胞被编程为在发育中的视叶的内侧边缘分化成神经母细胞。分化波在一排细胞中同步进行，从视叶的内侧区域到外侧区域，横扫整个神经上皮片;它之前是scute [l（1）sc]的前神经基因致死的瞬时表达，因此被称为前神经波。我们发现表皮生长因子受体（EGFR）信号通路促进前神经波的进展。EGFR信号在神经上皮细胞中被激活并诱导l（1）sc表达。表皮生长因子受体的激活是由Rhomboid（Rho）的瞬时表达调节的，这是EGF配体Spitz成熟所必需的。Rho表达也受到EGFR信号的调节。Rho的瞬时和空间限制性表达产生EGFR信号传导的顺序激活，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的表达由EGFR诱导，并且Notch信号传导抑制原神经状态。Notch信号传导活性通过其自身的反馈机制下调，该反馈机制允许处于前神经状态的细胞随后发育成成神经母细胞。因此，EGFR和Notch信号通路的协调顺序作用导致前神经波以精确有序的方式进展并诱导成神经细胞形成。
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.