Department of Biology, Stanford University, Stanford, CA 94305, USA.
Department of Biology, Stanford University, Stanford, CA 94305, USA; Department of Biological Sciences, San José State University, San José, CA 95192, USA.
Dev Cell. 2023 Oct 9;58(19):1830-1846.e12. doi: 10.1016/j.devcel.2023.07.008. Epub 2023 Aug 7.
Tissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. Using the C. elegans intestinal epithelium, we identified a patterning mechanism that is informed by cell contact lifetime asymmetry and executed via the scaffolding protein PAR-3 and the transmembrane protein E-cadherin/HMR-1. Intestinal cells break symmetry as PAR-3 and HMR-1 recruit apical determinants into punctate "local polarity complexes" (LPCs) at homotypic contacts. LPCs undergo an HMR-1-based migration to a common midline, thereby establishing tissue-wide polarity. Thus, symmetry breaking results from PAR-3-dependent intracellular polarization coupled to HMR-1-based tissue-level communication, which occurs through a non-adhesive signaling role for HMR-1. Differential lifetimes between homotypic and heterotypic cell contacts are created by neighbor exchanges and oriented divisions, patterning where LPCs perdure and thereby breaking symmetry. These cues offer a logical and likely conserved framework for how epithelia without obvious molecular asymmetries can polarize.
组织范围的模式形成对于多细胞发育至关重要，需要细胞单独生成极性轴，并在空间和时间上与相邻细胞进行协调。我们利用秀丽隐杆线虫的肠道上皮，确定了一种模式形成机制，该机制受细胞接触寿命不对称性的影响，并通过支架蛋白 PAR-3 和跨膜蛋白 E-cadherin/HMR-1 来执行。肠道细胞打破对称性，因为 PAR-3 和 HMR-1 将顶端决定因素募集到同质接触处的点状“局部极性复合物”（LPC）中。LPC 经历基于 HMR-1 的迁移到共同的中线，从而建立组织范围的极性。因此，对称性的破坏是由 PAR-3 依赖性的细胞内极化与基于 HMR-1 的组织水平通讯耦合引起的，这种通讯通过 HMR-1 的非粘着信号作用发生。同质和异质细胞接触之间的寿命差异是通过邻接交换和定向分裂产生的，LPC 持续存在的位置会破坏对称性。这些线索为没有明显分子不对称性的上皮如何极化提供了一个合理且可能保守的框架。
