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These pathways regulate lymphatic endothelial cell (LEC) migration, motility, polarity, and morphogenesis. Canonical and non\u2010canonical WNT signaling pathways are known to control LEC polarity and development of lymphatic vessels and valves.\n                      <jats:italic>PKD1<\/jats:italic>\n                      , encoding Polycystin\u20101, is the most commonly mutated gene in polycystic kidney disease but has also been shown to be essential in lymphatic vascular morphogenesis. The mechanism by which\n                      <jats:italic>Pkd1<\/jats:italic>\n                      acts during lymphangiogenesis remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here we find that loss of non\u2010canonical WNT signaling components\n                      <jats:italic>Wnt5a<\/jats:italic>\n                      and\n                      <jats:italic>Ryk<\/jats:italic>\n                      phenocopy lymphatic defects seen in\n                      <jats:italic>Pkd1<\/jats:italic>\n                      knockout mice. To investigate genetic interaction, we generated\n                      <jats:italic>Pkd1<\/jats:italic>\n                      ;\n                      <jats:italic>Wnt5a<\/jats:italic>\n                      double knockout mice. Loss of\n                      <jats:italic>Wnt5a<\/jats:italic>\n                      suppressed phenotypes seen in the lymphatic vasculature of\n                      <jats:italic>Pkd1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice and Pkd1 deletion suppressed phenotypes observed in\n                      <jats:italic>Wnt5a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice. Thus, we report mutually suppressive roles for\n                      <jats:italic>Pkd1<\/jats:italic>\n                      and\n                      <jats:italic>Wnt5a<\/jats:italic>\n                      , with developing lymphatic networks restored to a more wild type state in double mutant mice. This genetic interaction between\n                      <jats:italic>Pkd1<\/jats:italic>\n                      and the non\u2010canonical WNT signaling pathway ultimately controls LEC polarity and the morphogenesis of developing vessel networks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our work suggests that\n                      <jats:italic>Pkd1<\/jats:italic>\n                      acts at least in part by regulating non\u2010canonical WNT signaling during the formation of lymphatic vascular networks.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dvdy.390","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T10:06:45Z","timestamp":1624702005000},"page":"336-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>Pkd1<\/i>\n                    and\n                    <i>Wnt5a<\/i>\n                    genetically interact to control lymphatic vascular morphogenesis in mice"],"prefix":"10.1002","volume":"251","author":[{"given":"Tevin C. Y.","family":"Chau","sequence":"first","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungmin","family":"Baek","sequence":"additional","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baptiste","family":"Coxam","sequence":"additional","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renae","family":"Skoczylas","sequence":"additional","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Rondon\u2010Galeano","sequence":"additional","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"},{"name":"Organogenesis and Cancer Program Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil I.","family":"Bower","sequence":"additional","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elanor N.","family":"Wainwright","sequence":"additional","affiliation":[{"name":"Division of Genomics of Development and Disease, Institute for Molecular Bioscience The University of Queensland 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