Chang Weiru, Lloyd Christine E, Zarkower David
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Mech Dev. 2005 Jun;122(6):781-9. doi: 10.1016/j.mod.2005.03.005.
Like other organs, the C. elegans gonad develops from a simple primordium that must undergo axial patterning to generate correct adult morphology. Proximal/distal (PD) polarity in the C. elegans gonad is established early during gonadogenesis by the somatic gonad precursor cells, Z1 and Z4. Z1 and Z4 each divide asymmetrically to generate one daughter with a proximal fate and one with a distal fate. PD polarity of the Z1/Z4 lineages requires the activity of a Wnt pathway that activates the TCF/LEF homolog pop-1. How the gonadal pathway controlling pop-1 is regulated by upstream factors has been unclear, as neither Wnt nor Dishevelled (Dsh) proteins have been shown to be required. Here we show that the C. elegansdsh homolog dsh-2 controls gonadal polarity. As in pop-1 mutants, dsh-2 hermaphrodites have Z1 and Z4 lineage defects indicative of defective PD polarity and are missing gonadal arms. Males have an elongated but disorganized gonad, also with lineage defects. DSH-2 protein is expressed in the Z1/Z4 gonadal precursor cells. Asymmetric distribution of nuclear GFP::POP-1 in Z1 and Z4 daughter cells is reversed in dsh-2 mutants, with higher levels in distal than proximal daughters. dsh-2 and the frizzled receptor homolog lin-17 have a strong genetic interaction, suggesting that they act in a common pathway. We suggest that DSH-2 functions as an upstream regulator of POP-1 in the somatic gonad to control asymmetric cell division, thereby establishing proximal-distal polarity of the developing organ.
与其他器官一样，秀丽隐杆线虫的性腺由一个简单的原基发育而来，该原基必须经历轴向模式形成才能产生正确的成虫形态。秀丽隐杆线虫性腺中的近端/远端（PD）极性在性腺发生早期由体细胞性腺前体细胞Z1和Z4建立。Z1和Z4各自进行不对称分裂，产生一个具有近端命运的子代和一个具有远端命运的子代。Z1/Z4谱系的PD极性需要激活TCF/LEF同源物pop-1的Wnt信号通路的活性。目前尚不清楚控制pop-1的性腺信号通路是如何被上游因子调控的，因为尚未证明Wnt蛋白和Dishevelled（Dsh）蛋白是必需的。在这里，我们表明秀丽隐杆线虫的dsh同源物dsh-2控制性腺极性。与pop-1突变体一样，dsh-2雌雄同体具有Z1和Z4谱系缺陷，表明PD极性有缺陷，并且缺少性腺臂。雄性有一个细长但无序的性腺，也有谱系缺陷。DSH-2蛋白在Z1/Z4性腺前体细胞中表达。在dsh-2突变体中，Z1和Z4子代细胞中核GFP::POP-1的不对称分布发生逆转，远端子代中的水平高于近端子代。dsh-2和卷曲受体同源物lin-17具有很强的遗传相互作用，表明它们在共同的信号通路中起作用。我们认为DSH-2作为体细胞性腺中POP-1的上游调节因子，控制不对称细胞分裂，从而建立发育中器官的近端-远端极性。
