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Slit‐Robo signalling establishes a Sphingosine‐1‐phosphate gradient to polarise fin mesenchyme
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Mahabaleshwar, Harsha, Asharani, P. V., Loo, Tricia Yi, Koh, Shze Yung, Pitman, Melissa R., Kwok, Samuel, Ma, Jiajia, Hu, Bo, Lin, Fang, Li Lok, Xue, Pitson, Stuart M., Saunders, Timothy E. and Carney, Tom J. (2022) Slit‐Robo signalling establishes a Sphingosine‐1‐phosphate gradient to polarise fin mesenchyme. EMBO reports, 23 (8). e54464. doi:10.15252/embr.202154464 ISSN 1469-221X.
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WRAP-Slit‐robo-sphingosine‐1‐phosphate-polarise-fin-mesenchyme-morphology-2022.pdf - Accepted Version - Requires a PDF viewer. Download (556Kb) | Preview |
Official URL: https://doi.org/10.15252/embr.202154464
Abstract
Immigration of mesenchymal cells into the growing fin and limb buds drives distal outgrowth, with subsequent tensile forces between these cells essential for fin and limb morphogenesis. Morphogens derived from the apical domain of the fin, orientate limb mesenchyme cell polarity, migration, division and adhesion. The zebrafish mutant stomp displays defects in fin morphogenesis including blister formation and associated loss of orientation and adhesion of immigrating fin mesenchyme cells. Positional cloning of stomp identifies a mutation in the gene encoding the axon guidance ligand, Slit3. We provide evidence that Slit ligands derived from immigrating mesenchyme act via Robo receptors at the apical ectodermal ridge (AER) to promote release of sphingosine-1-phosphate (S1P). S1P subsequently diffuses back to the mesenchyme to promote their polarisation, orientation, positioning and adhesion to the interstitial matrix of the fin fold. We thus demonstrate the coordination of the Slit-Robo and S1P signalling pathways in fin fold morphogenesis. Our work introduces a mechanism regulating the orientation, positioning and adhesion of its constituent cells.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QL Zoology |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Mesenchyme, Mesenchymal stem cells , Fishes -- Morphogenesis, Cellular control mechanisms, Fins (Anatomy) -- Growth, Joints -- Growth, Zebra danio | |||||||||||||||
Journal or Publication Title: | EMBO reports | |||||||||||||||
Publisher: | Nature Publishing Group | |||||||||||||||
ISSN: | 1469-221X | |||||||||||||||
Official Date: | 3 August 2022 | |||||||||||||||
Dates: |
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Volume: | 23 | |||||||||||||||
Number: | 8 | |||||||||||||||
Article Number: | e54464 | |||||||||||||||
DOI: | 10.15252/embr.202154464 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Reuse Statement (publisher, data, author rights): | “This version of the article has been accepted for publication, after peer review but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.15252/embr.202154464. Use of this Accepted Version is subject to the publisher’s Accepted Manuscript terms of use https://www.springernature.com/gp/open-research/policies/acceptedmanuscript-terms”." | |||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||
Copyright Holders: | © 2022 The Authors | |||||||||||||||
Date of first compliant deposit: | 20 July 2022 | |||||||||||||||
Date of first compliant Open Access: | 9 December 2022 | |||||||||||||||
RIOXX Funder/Project Grant: |
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