ZFIN ID: ZDB-PUB-201002-93
RAB13 mRNA compartmentalisation spatially orients tissue morphogenesis
Costa, G., Bradbury, J.J., Tarannum, N., Herbert, S.P.
Date: 2020
Source: The EMBO journal   39(21): e106003 (Journal)
Registered Authors: Bradbury, Joshua, Costa, Guilherme, Herbert, Shane
Keywords: angiogenesis, endothelial cell, filopodia, mRNA targeting, zebrafish
Microarrays: GEO:GSE155449
MeSH Terms:
  • Animals
  • Cell Movement
  • Cell Polarity
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • GTP Phosphohydrolases
  • Gene Editing
  • Morphogenesis/genetics*
  • Morphogenesis/physiology*
  • Pseudopodia/metabolism
  • Pseudopodia/pathology
  • RNA, Messenger/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology
  • rab GTP-Binding Proteins/genetics*
  • rab GTP-Binding Proteins/metabolism*
PubMed: 32946121 Full text @ EMBO J.
Polarised targeting of diverse mRNAs to cellular protrusions is a hallmark of cell migration. Although a widespread phenomenon, definitive functions for endogenous targeted mRNAs and their relevance to modulation of in vivo tissue dynamics remain elusive. Here, using single-molecule analysis, gene editing and zebrafish live-cell imaging, we report that mRNA polarisation acts as a molecular compass that orients motile cell polarity and spatially directs tissue movement. Clustering of protrusion-derived RNAseq datasets defined a core 192-nt localisation element underpinning precise mRNA targeting to sites of filopodia formation. Such targeting of the small GTPase RAB13 generated tight spatial coupling of mRNA localisation, translation and protein activity, achieving precise subcellular compartmentalisation of RAB13 protein function to create a polarised domain of filopodia extension. Consequently, genomic excision of this localisation element and perturbation of RAB13 mRNA targeting-but not translation-depolarised filopodia dynamics in motile endothelial cells and induced mispatterning of blood vessels in zebrafish. Hence, mRNA polarisation, not expression, is the primary determinant of the site of RAB13 action, preventing ectopic functionality at inappropriate subcellular loci and orienting tissue morphogenesis.