Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/135621
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Type: Journal article
Title: Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme.
Author: Mahabaleshwar, H.
Asharani, P.V.
Loo, T.Y.
Koh, S.Y.
Pitman, M.R.
Kwok, S.
Ma, J.
Hu, B.
Lin, F.
Li Lok, X.
Pitson, S.M.
Saunders, T.E.
Carney, T.J.
Citation: EMBO Reports, 2022; e54464-e54464
Publisher: EMBO
Issue Date: 2022
ISSN: 1469-221X
1469-3178
Statement of
Responsibility: 
Harsha Mahabaleshwar, PV Asharani, Tricia Yi Loo, Shze Yung Koh, Melissa R Pitman, Samuel Kwok, Jiajia Ma, Bo Hu, Fang Lin, Xue Li Lok, Stuart M Pitson, Timothy E Saunders, Tom J Carney
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.
Keywords: fin
mesenchyme
Robo
Slit
sphingosine-1-phosphate
Description: OnlinePubl
Rights: © 2022 The Authors
DOI: 10.15252/embr.202154464
Grant ID: http://purl.org/au-research/grants/nhmrc/1042589
http://purl.org/au-research/grants/nhmrc/1156693
Appears in Collections:Biochemistry publications

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