Grimbert Stéphanie, Tietze Kyria, Barkoulas Michalis, Sternberg Paul W, Félix Marie-Anne, Braendle Christian
Centre National de la Recherche Scientifique (CNRS) UMR7277 - Institut National de la Santé et de la Recherche Médicale (INSERM) U1091, Université Nice Sophia Antipolis, 06108 Nice cedex 02, France.
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Dev Biol. 2016 Aug 1;416(1):123-135. doi: 10.1016/j.ydbio.2016.05.036. Epub 2016 Jun 8.
How cells coordinate their spatial positioning through intercellular signaling events is poorly understood. Here we address this topic using Caenorhabditis elegans vulval patterning during which hypodermal vulval precursor cells (VPCs) adopt distinct cell fates determined by their relative positions to the gonadal anchor cell (AC). LIN-3/EGF signaling by the AC induces the central VPC, P6.p, to adopt a 1° vulval fate. Exact alignment of AC and VPCs is thus critical for correct fate patterning, yet, as we show here, the initial AC-VPC positioning is both highly variable and asymmetric among individuals, with AC and P6.p only becoming aligned at the early L3 stage. Cell ablations and mutant analysis indicate that VPCs, most prominently 1° cells, move towards the AC. We identify AC-released LIN-3/EGF as a major attractive signal, which therefore plays a dual role in vulval patterning (cell alignment and fate induction). Additionally, compromising Wnt pathway components also induces AC-VPC alignment errors, with loss of posterior Wnt signaling increasing stochastic vulval centering on P5.p. Our results illustrate how intercellular signaling reduces initial spatial variability in cell positioning to generate reproducible interactions across tissues.
细胞如何通过细胞间信号事件协调其空间定位,目前还知之甚少。在这里,我们利用秀丽隐杆线虫的外阴模式形成来探讨这个问题,在此过程中,皮下外阴前体细胞(VPC)根据其与性腺锚定细胞(AC)的相对位置采用不同的细胞命运。AC发出的LIN-3/EGF信号诱导中央VPC,即P6.p,采用1°外阴命运。因此,AC和VPC的精确对齐对于正确的命运模式形成至关重要,然而,正如我们在此所示,初始AC-VPC定位在个体之间高度可变且不对称,AC和P6.p仅在L3早期阶段才对齐。细胞消融和突变分析表明,VPC,最显著的是1°细胞,向AC移动。我们确定AC释放的LIN-3/EGF是主要的吸引信号,因此在对外阴模式形成中起双重作用(细胞对齐和命运诱导)。此外,破坏Wnt信号通路成分也会诱导AC-VPC对齐错误,后Wnt信号的丧失会增加外阴随机以P5.p为中心的情况。我们的结果说明了细胞间信号如何减少细胞定位中的初始空间变异性,从而在组织间产生可重复的相互作用。