Laboratory of Morphogenesis, The Rockefeller University, New York, NY 10065, USA.
Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell. 2022 May 26;185(11):1960-1973.e11. doi: 10.1016/j.cell.2022.04.023. Epub 2022 May 11.
During vertebrate embryogenesis, cell collectives engage in coordinated behavior to form tissue structures of increasing complexity. In the avian skin, assembly into follicles depends on intrinsic mechanical forces of the dermis, but how cell mechanics initiate pattern formation is not known. Here, we reconstitute the initiation of follicle patterning ex vivo using only freshly dissociated avian dermal cells and collagen. We find that contractile cells physically rearrange the extracellular matrix (ECM) and that ECM rearrangement further aligns cells. This exchange transforms a mechanically unlinked collective of dermal cells into a continuum, with coherent, long-range order. Combining theory with experiment, we show that this ordered cell-ECM layer behaves as an active contractile fluid that spontaneously forms regular patterns. Our study illustrates a role for mesenchymal dynamics in generating cell-level ordering and tissue-level patterning through a fluid instability-processes that may be at play across morphological symmetry-breaking contexts.
在脊椎动物胚胎发生过程中，细胞集体通过协调行为形成结构越来越复杂的组织。在禽类皮肤中，滤泡的形成依赖于真皮的固有机械力，但细胞力学如何引发模式形成尚不清楚。在这里，我们仅使用新鲜分离的禽类真皮细胞和胶原蛋白在体外重建了滤泡模式形成的起始过程。我们发现收缩细胞会物理性地重新排列细胞外基质（ECM），而 ECM 的重新排列会进一步使细胞排列整齐。这种交换将一个机械上没有联系的真皮细胞集体转变为具有连贯的长程有序性的连续体。我们将理论与实验相结合，表明这个有序的细胞-细胞外基质层表现为一种主动收缩性流体，它会自发地形成规则的图案。我们的研究表明，间充质动力学在通过流体不稳定性产生细胞水平的有序性和组织水平的模式方面发挥了作用，而这种过程可能在形态对称破缺的情况下发挥作用。
