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, 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.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Baptiste
B
Coxam
Department of Oncology, University Hospital of Lausanne, and Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Amélie
A
Sabine
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Neil I
NI
Bower
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Kelly A
KA
Smith
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Cathy
C
Pichol-Thievend
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Renae
R
Skoczylas
Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, 1142 Auckland, New Zealand.
Jonathan W
JW
Astin
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Emmanuelle
E
Frampton
Department of Oncology, University Hospital of Lausanne, and Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Muriel
M
Jaquet
Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, 1142 Auckland, New Zealand.
Philip S
PS
Crosier
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Robert G
RG
Parton
Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia.
Natasha L
NL
Harvey
Department of Oncology, University Hospital of Lausanne, and Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Tatiana V
TV
Petrova
Hubrecht Institute-KNAW and UMC Utrecht, 3584CT Utrecht, the Netherlands.
Stefan
S
Schulte-Merker
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Mathias
M
Francois
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: b.hogan@imb.uq.edu.au.
Benjamin M
BM
Hogan
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008198:Lymph Nodes / Q000254:growth & development / Q000378:metabolism; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050396:TRPP Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D050396:TRPP Cation Channels; D029961:Zebrafish Proteins