PUBLICATION
Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis
- Authors
- Munjal, A., Hannezo, E., Tsai, T.Y., Mitchison, T.J., Megason, S.G.
- ID
- ZDB-PUB-211224-27
- Date
- 2021
- Source
- Cell 184: 6313-6325.e18 (Journal)
- Registered Authors
- Megason, Sean, Munjal, Akankshi, Tsai, Tony
- Keywords
- ECM, actomyosin, cadherin, hyaluronan, hyaluronic acid, hydraulics, inner ear, semicircular canals, tissue morphogenesis, zebrafish
- MeSH Terms
-
- Actomyosin/metabolism
- Animals
- Anisotropy
- Behavior, Animal
- Extracellular Matrix/metabolism
- Extracellular Space/chemistry*
- Hyaluronic Acid/biosynthesis
- Hyaluronic Acid/pharmacology*
- Models, Biological
- Morphogenesis*/drug effects
- Organ Specificity*/drug effects
- Osmotic Pressure
- Pressure*
- Semicircular Canals/cytology*
- Semicircular Canals/diagnostic imaging
- Semicircular Canals/embryology*
- Stereotyped Behavior
- Zebrafish/embryology
- Zebrafish Proteins/metabolism
- PubMed
- 34942099 Full text @ Cell
Citation
Munjal, A., Hannezo, E., Tsai, T.Y., Mitchison, T.J., Megason, S.G. (2021) Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis. Cell. 184:6313-6325.e18.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping