PUBLICATION
Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme
- Authors
- 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.
- ID
- ZDB-PUB-220610-6
- Date
- 2022
- Source
- EMBO reports 23(8): e54464 (Journal)
- Registered Authors
- Carney, Tom, Kwok, Samuel, Lin, Fang, Loo, Tricia, Mahabaleshwar, Harsha, Saunders, Timothy Edward
- Keywords
- Robo, Slit, fin, mesenchyme, sphingosine-1-phosphate
- MeSH Terms
-
- Animals
- Gene Expression Regulation, Developmental*
- Intracellular Signaling Peptides and Proteins/genetics
- Lysophospholipids
- Mesoderm/metabolism
- Sphingosine/analogs & derivatives
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35679135 Full text @ EMBO Rep.
Citation
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. (2022) Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme. EMBO reports. 23(8):e54464.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping