ZFIN ID: ZDB-PUB-140513-85
Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development
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.
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.
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.