LIN-39 and the EGFR/RAS/MAPK pathway regulate C-elegans vulval morphogenesis via the VAB-23 zinc finger protein
LIN-39 and the EGFR/RAS/MAPK pathway regulate C-elegans vulval morphogenesis via the VAB-23 zinc finger protein
复制标题
DOI：
10.1242/dev.071951
复制
发表时间：
2011-11-01
期刊：
影响因子：
4.6
通讯作者：
Hajnal, Alex
中科院分区：
文献类型：
--
作者：
Pellegrino, Mark W.;Farooqui, Sarfarazhussain;Hajnal, Alex
形态发生是细胞命运决定的一个发育阶段。保守的hox基因是后生动物发育过程中关键的细胞命运决定因子，但其在控制器官形态发生中的作用尚不清楚。在这里，我们表明，C。elegans hox基因lin-39通过其新靶点--必需锌指蛋白VAB-23调节表皮形态发生。在雌雄同体的产卵器官外阴的发育过程中，EGFR/RAS/MAPK信号通路与LIN-39 HOX一起激活VAB-23在原代细胞谱系中的表达，以控制七个外阴环的形成。VAB-23通过诱导smp-1（脑信号蛋白）转录调节外阴中线处具有相同亚命运的对侧细胞对之间同型接触的形成。此外，VAB-23通过负调节融合因子eff-1的表达来防止异位外阴细胞融合。因此，LIN-39和EGFR/RAS/MAPK信号通路在外阴诱导期间较早地指定细胞命运，通过调节表皮形态发生的各个方面在细胞命运执行的后续阶段期间继续起作用。因此，外阴细胞命运的规范和执行是紧密耦合的过程。
Morphogenesis represents a phase of development during which cell fates are executed. The conserved hox genes are key cell fate determinants during metazoan development, but their role in controlling organ morphogenesis is less understood. Here, we show that the C. elegans hox gene lin-39 regulates epidermal morphogenesis via its novel target, the essential zinc finger protein VAB-23. During the development of the vulva, the egg-laying organ of the hermaphrodite, the EGFR/RAS/MAPK signaling pathway activates, together with LIN-39 HOX, the expression of VAB-23 in the primary cell lineage to control the formation of the seven vulval toroids. VAB-23 regulates the formation of homotypic contacts between contralateral pairs of cells with the same sub-fates at the vulval midline by inducing smp-1 (semaphorin) transcription. In addition, VAB-23 prevents ectopic vulval cell fusions by negatively regulating expression of the fusogen eff-1. Thus, LIN-39 and the EGFR/RAS/MAPK signaling pathway, which specify cell fates earlier during vulval induction, continue to act during the subsequent phase of cell fate execution by regulating various aspects of epidermal morphogenesis. Vulval cell fate specification and execution are, therefore, tightly coupled processes.