RRC ID 76496
Author Wang G, Muhl L, Padberg Y, Dupont L, Peterson-Maduro J, Stehling M, le Noble F, Colige A, Betsholtz C, Schulte-Merker S, van Impel A.
Title Specific fibroblast subpopulations and neuronal structures provide local sources of Vegfc-processing components during zebrafish lymphangiogenesis.
Journal Nat Commun
Abstract Proteolytical processing of the growth factor VEGFC through the concerted activity of CCBE1 and ADAMTS3 is required for lymphatic development to occur. How these factors act together in time and space, and which cell types produce these factors is not understood. Here we assess the function of Adamts3 and the related protease Adamts14 during zebrafish lymphangiogenesis and show both proteins to be able to process Vegfc. Only the simultaneous loss of both protein functions results in lymphatic defects identical to vegfc loss-of-function situations. Cell transplantation experiments demonstrate neuronal structures and/or fibroblasts to constitute cellular sources not only for both proteases but also for Ccbe1 and Vegfc. We further show that this locally restricted Vegfc maturation is needed to trigger normal lymphatic sprouting and directional migration. Our data provide a single-cell resolution model for establishing secretion and processing hubs for Vegfc during developmental lymphangiogenesis.
Volume 11(1)
Pages 2724
Published 2020-6-1
DOI 10.1038/s41467-020-16552-7
PII 10.1038/s41467-020-16552-7
PMID 32483144
PMC PMC7264274
MeSH ADAMTS Proteins / genetics ADAMTS Proteins / metabolism Animals Animals, Genetically Modified Fibroblasts / metabolism* Gene Expression Regulation, Developmental HEK293 Cells Humans Lymphangiogenesis / genetics* Lymphatic Vessels / embryology Lymphatic Vessels / metabolism Microscopy, Confocal Neurons / metabolism* Procollagen N-Endopeptidase / genetics Procollagen N-Endopeptidase / metabolism Vascular Endothelial Growth Factor C / genetics* Vascular Endothelial Growth Factor C / metabolism Zebrafish / embryology Zebrafish / genetics* Zebrafish / metabolism Zebrafish Proteins / genetics* Zebrafish Proteins / metabolism
IF 12.121
Zebrafish UAS:GFP, UAS:RFP