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Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis
Akankshi Munjal1, Edouard Hannezo2, Tony Y-C Tsai1
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 23, 2021
Summary
Zebrafish semicircular canal formation relies on hyaluronan secretion, not actomyosin forces. This extracellular pressure shapes tissues, inverting typical models of organogenesis.
Area of Science:
- Developmental Biology
- Regenerative Medicine
- Biophysics
Background:
- Understanding tissue morphogenesis is crucial for biology and regenerative medicine.
- Conventional models often attribute tissue shaping to actomyosin contractility.
- The role of the extracellular matrix in driving morphogenesis is less understood.
Purpose of the Study:
- To investigate the mechanisms underlying zebrafish semicircular canal formation.
- To determine the role of actomyosin and extracellular matrix in this process.
- To explore novel mechanisms of organogenesis and tissue engineering.
Main Methods:
- Analysis of zebrafish otic epithelium development.
- Investigation of hyaluronan secretion and its enzymatic regulation (ugdh, has3).
- Characterization of mechanical forces, including extracellular pressure and cytocinches.
Main Results:
- Zebrafish semicircular canal morphogenesis is independent of conventional actomyosin-driven behaviors.
- Local hyaluronan secretion by uridine 5'-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3) drives bud formation.
- Charged hyaluronate polymers generate osmotic pressure, deforming the epithelium.
- Polarized actomyosin and E-cadherin tethers (cytocinches) confer mechanical anisotropy for tube shaping.
Conclusions:
- This study inverts the traditional view of morphogenesis, highlighting hyaluronan pressure as a primary driver.
- Anisotropic tissue stiffness modulates hyaluronate pressure for precise shape control.
- This mechanism offers a new perspective on organogenesis and potential applications in tissue engineering.
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