---
_id: '10573'
abstract:
- lang: eng
  text: 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.
acknowledgement: We thank Ian Swinburne, Sandy Nandagopal, and Toru Kawanishi for
  support, discussions, and reagents. We thank Vanessa Barone, Joseph Nasser, and
  members of the Megason lab for useful comments on the manuscript and general feedback.
  We are grateful to the Heisenberg and Knaut labs for transgenic fish. Diagrams on
  the right in the graphical abstract were created using BioRender. This work was
  supported by NIH R01DC015478 and NIH R01GM107733 to S.G.M. A.M. was supported by
  Human Frontiers Science Program LTF and NIH K99HD098918.
article_processing_charge: No
article_type: original
author:
- first_name: Akankshi
  full_name: Munjal, Akankshi
  last_name: Munjal
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Tony Y.C.
  full_name: Tsai, Tony Y.C.
  last_name: Tsai
- first_name: Timothy J.
  full_name: Mitchison, Timothy J.
  last_name: Mitchison
- first_name: Sean G.
  full_name: Megason, Sean G.
  last_name: Megason
citation:
  ama: Munjal A, Hannezo EB, Tsai TYC, Mitchison TJ, Megason SG. Extracellular hyaluronate
    pressure shaped by cellular tethers drives tissue morphogenesis. <i>Cell</i>.
    2021;184(26):6313-6325.e18. doi:<a href="https://doi.org/10.1016/j.cell.2021.11.025">10.1016/j.cell.2021.11.025</a>
  apa: Munjal, A., Hannezo, E. B., Tsai, T. Y. C., Mitchison, T. J., &#38; Megason,
    S. G. (2021). Extracellular hyaluronate pressure shaped by cellular tethers drives
    tissue morphogenesis. <i>Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.cell.2021.11.025">https://doi.org/10.1016/j.cell.2021.11.025</a>
  chicago: Munjal, Akankshi, Edouard B Hannezo, Tony Y.C. Tsai, Timothy J. Mitchison,
    and Sean G. Megason. “Extracellular Hyaluronate Pressure Shaped by Cellular Tethers
    Drives Tissue Morphogenesis.” <i>Cell</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.cell.2021.11.025">https://doi.org/10.1016/j.cell.2021.11.025</a>.
  ieee: A. Munjal, E. B. Hannezo, T. Y. C. Tsai, T. J. Mitchison, and S. G. Megason,
    “Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis,”
    <i>Cell</i>, vol. 184, no. 26. Elsevier, p. 6313–6325.e18, 2021.
  ista: Munjal A, Hannezo EB, Tsai TYC, Mitchison TJ, Megason SG. 2021. Extracellular
    hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis. Cell.
    184(26), 6313–6325.e18.
  mla: Munjal, Akankshi, et al. “Extracellular Hyaluronate Pressure Shaped by Cellular
    Tethers Drives Tissue Morphogenesis.” <i>Cell</i>, vol. 184, no. 26, Elsevier,
    2021, p. 6313–6325.e18, doi:<a href="https://doi.org/10.1016/j.cell.2021.11.025">10.1016/j.cell.2021.11.025</a>.
  short: A. Munjal, E.B. Hannezo, T.Y.C. Tsai, T.J. Mitchison, S.G. Megason, Cell
    184 (2021) 6313–6325.e18.
date_created: 2021-12-26T23:01:26Z
date_published: 2021-12-22T00:00:00Z
date_updated: 2025-05-14T11:26:20Z
day: '22'
department:
- _id: EdHa
doi: 10.1016/j.cell.2021.11.025
external_id:
  isi:
  - '000735387500002'
intvolume: '       184'
isi: 1
issue: '26'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.biorxiv.org/content/10.1101/2020.09.28.316042
month: '12'
oa: 1
oa_version: Preprint
page: 6313-6325.e18
publication: Cell
publication_identifier:
  eissn:
  - 1097-4172
  issn:
  - 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Extracellular hyaluronate pressure shaped by cellular tethers drives tissue
  morphogenesis
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 184
year: '2021'
...