Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis.

Journal Article (Journal Article)

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 uridine 5'-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (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 may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.

Full Text

Duke Authors

Cited Authors

  • Munjal, A; Hannezo, E; Tsai, TY-C; Mitchison, TJ; Megason, SG

Published Date

  • December 22, 2021

Published In

Volume / Issue

  • 184 / 26

Start / End Page

  • 6313 - 6325.e18

PubMed ID

  • 34942099

Pubmed Central ID

  • PMC8722442

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2021.11.025


  • eng

Conference Location

  • United States