Soulard Maleaume, Contreras Diego Andrés, Monier Bruno, Mangeat Thomas, Dougados Vanessa, Zanet Jennifer, Corson Francis, Hakim Vincent, Payre François, Pélissier-Monier Anne
Molecular Cellular and Developmental Biology (MCD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31000 Toulouse, France.
Laboratoire de Physique de l'Ecole Normale Supérieure, CNRS, Ecole Normale Supérieure, PSL University, Sorbonne Université, Université Paris Cité, Paris, France.
iScience. 2025 Jul 17;28(8):113135. doi: 10.1016/j.isci.2025.113135. eCollection 2025 Aug 15.
During animal development, cells communicate to ensure tissue-wide synchronization of differentiation. While several mechanisms contributing to cell coordination have been described, whether additional mechanisms are at play should cells locally desynchronize remains unknown. Here, we investigate the responses to experimentally induced desynchronized cells during epidermis development. We report that cells that behave as if they were "too young" or "too old", collectively referred to as heterochronous cells, sort out from their normally timed neighbors. Cell sorting is associated with alterations of junctions, cytoskeleton, and cell mechanics. Moreover, local heterochrony ultimately leads to cell elimination. Importantly, we find that some cells naturally undergo either premature or delayed differentiation during development and are similarly eliminated from the tissue. These results show that local imbalance in differentiation timing affects both cell interactions and mechanics, leading to cell sorting, and elimination as a way to correct local heterochrony and safeguard the synchrony of epithelium differentiation.
在动物发育过程中,细胞相互通讯以确保全组织范围内分化的同步性。虽然已经描述了几种有助于细胞协调的机制,但当细胞局部去同步时是否有其他机制发挥作用仍然未知。在这里,我们研究了表皮发育过程中对实验诱导的去同步细胞的反应。我们报告称,那些表现得“太年轻”或“太老”的细胞,统称为异时细胞,会从正常时间发育的邻居中分离出来。细胞分选与连接、细胞骨架和细胞力学的改变有关。此外,局部异时最终导致细胞消除。重要的是,我们发现一些细胞在发育过程中自然会经历过早或延迟分化,并且同样会从组织中被消除。这些结果表明,分化时间的局部失衡会影响细胞相互作用和力学,导致细胞分选和消除,以此来纠正局部异时并保障上皮分化的同步性。