Pkd1 regulates lymphatic vascular morphogenesis during development

Baptiste Coxam; Amélie Sabine; Neil I Bower; Kelly A Smith; Cathy Pichol-Thievend; Renae Skoczylas; Jonathan W Astin; Emmanuelle Frampton; Muriel Jaquet; Philip S Crosier; Robert G Parton; Natasha L Harvey; Tatiana V Petrova; Stefan Schulte-Merker; Mathias Francois; Benjamin M Hogan

doi:10.1016/j.celrep.2014.03.063

Pkd1 regulates lymphatic vascular morphogenesis during development

Baptiste Coxam, Amélie Sabine, Neil I Bower, Kelly A Smith, Cathy Pichol-Thievend, Renae Skoczylas, Jonathan W Astin, Emmanuelle Frampton, Muriel Jaquet, Philip S Crosier, Robert G Parton, Natasha L Harvey, Tatiana V Petrova, Stefan Schulte-Merker, Mathias Francois, Benjamin M Hogan

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

71 Citations (Scopus)

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.

Original language	English
Pages (from-to)	623-33
Number of pages	11
Journal	Cell Reports
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2014.03.063
Publication status	Published - 08 May 2014

Keywords

Animals
Animals, Genetically Modified
Cells, Cultured
Embryo, Mammalian
Embryonic Development
Endothelial Cells
Humans
Intercellular Junctions
Lymph Nodes
Lymphangiogenesis
Lymphatic Vessels
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Phenotype
Polycystic Kidney, Autosomal Dominant
TRPP Cation Channels
Zebrafish
Zebrafish Proteins

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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. (2014). Pkd1 regulates lymphatic vascular morphogenesis during development. Cell Reports, 7(3), 623-33. https://doi.org/10.1016/j.celrep.2014.03.063

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title = "Pkd1 regulates lymphatic vascular morphogenesis during development",

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.",

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author = "Baptiste Coxam and Am{\'e}lie Sabine and Bower, {Neil I} and Smith, {Kelly A} and Cathy Pichol-Thievend and Renae Skoczylas and Astin, {Jonathan W} and Emmanuelle Frampton and Muriel Jaquet and Crosier, {Philip S} and Parton, {Robert G} and Harvey, {Natasha L} and Petrova, {Tatiana V} and Stefan Schulte-Merker and Mathias Francois and Hogan, {Benjamin M}",

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doi = "10.1016/j.celrep.2014.03.063",

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AU - Coxam, Baptiste

AU - Sabine, Amélie

AU - Bower, Neil I

AU - Smith, Kelly A

AU - Pichol-Thievend, Cathy

AU - Skoczylas, Renae

AU - Astin, Jonathan W

AU - Frampton, Emmanuelle

AU - Jaquet, Muriel

AU - Crosier, Philip S

AU - Parton, Robert G

AU - Harvey, Natasha L

AU - Petrova, Tatiana V

AU - Schulte-Merker, Stefan

AU - Francois, Mathias

AU - Hogan, Benjamin M

PY - 2014/5/8

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N2 - 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.

AB - 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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KW - Animals, Genetically Modified

KW - Cells, Cultured

KW - Embryo, Mammalian

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KW - Endothelial Cells

KW - Humans

KW - Intercellular Junctions

KW - Lymph Nodes

KW - Lymphangiogenesis

KW - Lymphatic Vessels

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Mutation

KW - Phenotype

KW - Polycystic Kidney, Autosomal Dominant

KW - TRPP Cation Channels

KW - Zebrafish

KW - Zebrafish Proteins

U2 - 10.1016/j.celrep.2014.03.063

DO - 10.1016/j.celrep.2014.03.063

M3 - Article

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SN - 2211-1247

VL - 7

SP - 623

EP - 633

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

Pkd1 regulates lymphatic vascular morphogenesis during development

Abstract

Keywords

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