Slit‐Robo signalling establishes a Sphingosine‐1‐phosphate gradient to polarise fin mesenchyme

Harsha Mahabaleshwar; P V 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

doi:10.15252/embr.202154464

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Slit‐Robo signalling establishes a Sphingosine‐1‐phosphate gradient to polarise fin mesenchyme

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Slit‐Robo signalling establishes a Sphingosine‐1‐phosphate gradient to polarise fin mesenchyme

Harsha Mahabaleshwar, P V Asharani, Tricia Yi Loo, Shze Yung Koh, Melissa R Pitman, Samuel Kwok, Jiajia Ma, Bo Hu, Fang Lin, Xue Li Lok, …

EMBO reports, Vol.23(8), pp.e54464-n/a

06/09/2022

DOI: 10.15252/embr.202154464

PMCID: PMC9346495

PMID: 35679135

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https://www.ncbi.nlm.nih.gov/pmc/articles/9346495View

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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.

Details

Title: Subtitle: Slit‐Robo signalling establishes a Sphingosine‐1‐phosphate gradient to polarise fin mesenchyme
Creators: Harsha Mahabaleshwar - Nanyang Technological University
P V Asharani - Institute of Molecular and Cell Biology (IMCB) A*STAR (Agency for Science, Technology and Research) Singapore City Singapore
Tricia Yi Loo - National University of Singapore
Shze Yung Koh - Nanyang Technological University
Melissa R Pitman - The University of Adelaide
Samuel Kwok - Nanyang Technological University
Jiajia Ma - Nanyang Technological University
Bo Hu - University of Iowa
Fang Lin - University of Iowa
Xue Li Lok - Institute of Molecular and Cell Biology (IMCB) ASTAR (Agency for Science, Technology and Research) Singapore City Singapore
Stuart M Pitson - University of South Australia
Timothy E Saunders - National University of Singapore
Tom J Carney - Nanyang Technological University
Resource Type: Journal article
Publication Details: EMBO reports, Vol.23(8), pp.e54464-n/a
DOI: 10.15252/embr.202154464
PMID: 35679135
PMCID: PMC9346495
NLM abbreviation: EMBO Rep
ISSN: 1469-221X
eISSN: 1469-3178
Grant note: DOI: 10.13039/100000001, name: National Science Foundation, award: IOS‐1354457; DOI: 10.13039/501100000925, name: National Health and Medical Research Council, award: 1042589, 1156693
Language: English
Date published: 06/09/2022
Academic Unit: Anatomy and Cell Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984288756502771

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