The University of Melbourne, Department of Veterinary Science, Werribee, Victoria, Australia.
Development. 2011 Nov;138(21):4649-60. doi: 10.1242/dev.071951.
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.
形态发生是一个细胞命运得以执行的发育阶段。保守的同源盒基因是后生动物发育过程中关键的细胞命运决定因素，但它们在控制器官形态发生中的作用还不太清楚。在这里，我们表明，秀丽隐杆线虫的 hox 基因 lin-39 通过其新的靶标，必需的锌指蛋白 VAB-23，来调节表皮形态发生。在雌性的产卵器官——阴门的发育过程中，表皮生长因子受体/ Ras/ MAPK 信号通路与 LIN-39 HOX 一起被激活，在原始细胞谱系中表达 VAB-23，以控制七个阴门环的形成。VAB-23 通过诱导 smp-1（神经丝蛋白）转录，调节在阴门中线具有相同亚命运的对侧细胞之间的同源接触的形成。此外，VAB-23 通过负调控融合基因 eff-1 的表达来防止异位阴门细胞融合。因此，LIN-39 和表皮生长因子受体/ Ras/ MAPK 信号通路在阴门诱导的早期指定细胞命运，通过调节表皮形态发生的各个方面，在随后的细胞命运执行阶段继续发挥作用。因此，阴门细胞命运的指定和执行是紧密耦联的过程。
