Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development
Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhe...
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Published in | Cell reports (Cambridge) Vol. 7; no. 3; pp. 623 - 633 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.05.2014
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhesion, mixing, regression, and shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. A mutation in polycystic kidney disease 1a was responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial lymphatic precursor sprouting is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice has no effect on precursor sprouting but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation, and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development.
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•Identification of an unexpected role for the ADPKD gene Pkd1 in lymphatic development•Pkd1 regulates endothelial cell sprouting and cell-cell junctions in vitro•Pkd1 regulates cell polarity and cell-cell junctions in developing vessels in mice
The earliest steps in lymphatic vascular development are increasingly well defined, but the processes and molecules that control ongoing network morphogenesis remain to be understood. In this study, Coxam et al. show that the autosomal dominant polycystic kidney disease (ADPKD) gene Pkd1 regulates lymphatic endothelial cell polarity, shape, and adhesion during migration, vessel morphogenesis, and lymphatic vascular network elaboration. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Joint last authors |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2014.03.063 |