Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis.

Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis.
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DOI:
10.1016/j.cell.2021.11.025
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发表时间:
2021-12-22
期刊:
影响因子:
64.5
通讯作者:
Megason SG
Megason SG
中科院分区:
生物学1区
文献类型:
--
作者:
Munjal A;Hannezo E;Tsai TY;Mitchison TJ;Megason SG

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组织如何获得复杂的形状是生物学和再生医学中的一个基本问题。斑马鱼半规管由耳上皮(芽)的内陷形成,这些内陷延伸并融合形成每个半规管的枢纽。我们发现不需要传统的肌动球蛋白驱动行为。相反,由酶ugdh和has3产生的透明质酸的局部分泌,驱动了根管的形态发生。带电的透明质酸盐聚合物遇水膨胀,产生各向同性的细胞外压力,使上覆上皮变形成芽。机械各向异性需要塑造芽管赋予的极化分布的肌动球蛋白和E-钙粘蛋白丰富的膜系,我们的术语cytocinches。大多数关于组织形态发生的工作都将肌动球蛋白收缩性归因为驱动力,而细胞外基质通过不同的刚度来塑造组织。我们的工作扭转了这种期望。由各向异性组织刚度形成的超声波压力可能是器官发生和组织工程中动力形态变化的普遍机制。Munjal等人提出的证据表明,细胞外基质可以提供形成组织形态发生的驱动力。具体地说,他们表明,透明质酸压力,由各向异性组织刚度形成,是一种动力形态变化的机制。
How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes ugdh and has3, drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-Cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate-pressure shaped by anisotropic tissue stiffness maybe a widespread mechanism for powering morphological change in organogenesis and tissue engineering. Munjal et al. present evidence that the extracellular matrix can provide the driving force to shape tissue morphogenesis. Specifically, they show that hyaluronate-pressure, shaped by anisotropic tissue stiffness, is a mechanism for powering morphological change.
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