<i>pix-1</i> Controls Early Elongation in Parallel with <i>mel-11</i> and <i>let-502</i> in <i>Caenorhabditis elegans</i>

Cell shape changes are crucial for metazoan development. During Caenorhabditis elegans embryogenesis, epidermal cell shape changes transform ovoid embryos into vermiform larvae. This process is divided into two phases: early and late elongation. Early elongation involves the contraction of filamentous actin bundles by phosphorylated non-muscle myosin in a subset of epidermal (hypodermal) cells. The genes controlling early elongation are associated with two parallel pathways. The first one involves the rho-1/RHOA-specific effector let-502/Rho-kinase and mel-11/myosin phosphatase regulatory subunit. The second pathway involves the CDC42/RAC-specific effector pak-1. Late elongation is driven by mechanotransduction in ventral and dorsal hypodermal cells in response to body-wall muscle contractions, and involves the CDC42/RAC-specific Guanine-nucleotide Exchange Factor (GEF) pix-1, the GTPase ced-10/RAC and pak-1. In this study, pix-1 is shown to control early elongation in parallel with let-502/mel-11, as previously shown for pak-1. We show that pix-1, pak-1 and let-502 control the rate of elongation, and the antero-posterior morphology of the embryos. In particular, pix-1 and pak-1 are shown to control head, but not tail width, while let-502 controls both head and tail width. This suggests that let-502 function is required throughout the antero-posterior axis of the embryo during early elongation, while pix-1/pak-1 function may be mostly required in the anterior part of the embryo. Supporting this hypothesis we show that low pix-1 expression level in the dorsal-posterior hypodermal cells is required to ensure high elongation rate during early elongation.细胞形态变化对于后生动物发育至关重要。在秀丽隐杆线虫（Caenorhabditis elegans）胚胎发生过程中，表皮（皮下）细胞的形态变化将卵形胚胎转化为线形幼虫。该过程可分为两个阶段：早期伸长与晚期伸长。早期伸长涉及部分表皮（皮下）细胞中，磷酸化非肌肉肌球蛋白对丝状肌动蛋白束的收缩作用。调控早期伸长的基因关联两条平行通路：第一条通路涉及rho-1/RHOA特异性效应因子let-502/Rho激酶与mel-11/肌球蛋白磷酸酶调节亚基；第二条通路涉及CDC42/RAC特异性效应因子pak-1。晚期伸长则由腹侧与背侧皮下细胞响应体壁肌肉收缩的机械转导过程驱动，该过程涉及鸟苷酸交换因子（Guanine-nucleotide Exchange Factor, GEF）pix-1、GTP酶ced-10/RAC与pak-1。 本研究证实，pix-1可与let-502/mel-11协同调控早期伸长，正如此前关于pak-1的研究结论。我们发现pix-1、pak-1与let-502均可调控胚胎伸长速率与前后形态。具体而言，pix-1与pak-1仅调控头部宽度而非尾部宽度，而let-502则同时调控头部与尾部宽度。这提示在早期伸长阶段，let-502的功能在胚胎前后轴上广泛发挥作用，而pix-1/pak-1的功能则主要集中于胚胎前部。为验证这一假说，我们证实：背侧后部皮下细胞中较低的pix-1表达水平，是保障早期伸长阶段高伸长速率的必要条件。