Open AccessLocalised Collagen2a1 secretion supports lymphatic endothelial cell migration in the zebrafish embryo
Author(s) -
Smrita Chaudhury,
Kazuhide S. Okuda,
Katarzyna Koltowska,
Anne Karine Lagendijk,
Scott Paterson,
Gregory J. Baillie,
Cas Simons,
K. A. Smith,
Benjamin M. Hogan,
Neil I. Bower
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.190983
Subject(s) - biology , zebrafish , secretion , microbiology and biotechnology , lymphatic system , embryo , lymphatic endothelium , genetics , immunology , gene , endocrinology
The lymphatic vasculature develops primarily from pre-existing veins. A pool of lymphatic endothelial cells (LECs) first sprout from cardinal veins followed by migration and proliferation to colonise embryonic tissues. While much is known about the molecular regulation of LEC fate and sprouting during early lymphangiogenesis, we know far less about the instructive and permissive signals that support LEC migration through the embryo. Using a forward genetic screen, we identified mbtps1 and sec23a, components of the COP-II protein secretory pathway, as essential for developmental lymphangiogenesis. In both mutants, LECs initially depart the cardinal vein but then fail in their ongoing migration. A key cargo that failed to be secreted in both mutants was a type II collagen (Col2a1). Col2a1 is normally secreted by notochord sheath cells alongside which LECs migrate. col2a1a mutants displayed defects in the migratory behaviour of LECs and failed lymphangiogenesis. These studies thus identify Col2a1 as a key cargo secreted by notochord sheath cells and required for the migration of LECs. These findings combine with our current understanding to suggest that successive cell-to-cell and cell-matrix interactions regulate the migration of LECs through the embryonic environment during development.