PUBLICATION

Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development

Authors
Coxam, B., Sabine, A., Bower, N.I., Smith, K.A., Pichol-Thievend, C., Skoczylas, R., Astin, J.W., Frampton, E., Jaquet, M., Crosier, P.S., Parton, R.G., Harvey, N.L., Petrova, T.V., Schulte-Merker, S., Francois, M., Hogan, B.M.
ID
ZDB-PUB-140513-85
Date
2014
Source
Cell Reports   7: 623-33 (Journal)
Registered Authors
Coxam, Baptiste, Crosier, Phil, Hogan, Ben M., Parton, Robert G., Schulte-Merker, Stefan, Smith, Kelly
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Embryo, Mammalian/metabolism
  • Embryonic Development
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • Humans
  • Intercellular Junctions/metabolism
  • Lymph Nodes/growth & development
  • Lymph Nodes/metabolism
  • Lymphangiogenesis*
  • Lymphatic Vessels/metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Phenotype
  • Polycystic Kidney, Autosomal Dominant/genetics
  • Polycystic Kidney, Autosomal Dominant/metabolism
  • Polycystic Kidney, Autosomal Dominant/pathology
  • TRPP Cation Channels/antagonists & inhibitors
  • TRPP Cation Channels/genetics
  • TRPP Cation Channels/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
24767999 Full text @ Cell Rep.
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes