{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Britto DD"],"funding":["Marsden Fund","Leukaemia and Blood Cancer New Zealand","Royal Society of New Zealand","NCRR NIH HHS","Family of Marijana Kumerich","NHLBI NIH HHS","National Institutes of Health","Health Research Council of New Zealand"],"pagination":["dev200560"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9720674"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["149(21)"],"pubmed_abstract":["Lymphangiogenesis is a dynamic process that involves the directed migration of lymphatic endothelial cells (LECs) to form lymphatic vessels. The molecular mechanisms that underpin lymphatic vessel patterning are not fully elucidated and, to date, no global regulator of lymphatic vessel guidance is known. In this study, we identify the transmembrane cell signalling receptor Plexin D1 (Plxnd1) as a negative regulator of both lymphatic vessel guidance and lymphangiogenesis in zebrafish. plxnd1 is expressed in developing lymphatics and is required for the guidance of both the trunk and facial lymphatic networks. Loss of plxnd1 is associated with misguided intersegmental lymphatic vessel growth and aberrant facial lymphatic branches. Lymphatic guidance in the trunk is mediated, at least in part, by the Plxnd1 ligands, Semaphorin 3AA and Semaphorin 3C. Finally, we show that Plxnd1 normally antagonises Vegfr/Erk signalling to ensure the correct number of facial LECs and that loss of plxnd1 results in facial lymphatic hyperplasia. As a global negative regulator of lymphatic vessel development, the Sema/Plxnd1 signalling pathway is a potential therapeutic target for treating diseases associated with dysregulated lymphatic growth."],"journal":["Development (Cambridge, England)"],"pubmed_title":["Plexin D1 negatively regulates zebrafish lymphatic development."],"pmcid":["PMC9720674"],"funding_grant_id":["1R01HL161090-01A1","R01 HL133687","UOA1602","S10 RR024708","14/105","20-UOA-27","R01 HL161090","5R01HL133687"],"pubmed_authors":["Herbert CD","Astin JW","Hall CJ","He J","Crosier KE","Kakadia PM","Britto DD","Hogan BM","Misa JP","Crosier PS","Grimm L","Bohlander SK","Chen W","Torres-Vazquez J"],"additional_accession":[]},"is_claimable":false,"name":"Plexin D1 negatively regulates zebrafish lymphatic development.","description":"Lymphangiogenesis is a dynamic process that involves the directed migration of lymphatic endothelial cells (LECs) to form lymphatic vessels. The molecular mechanisms that underpin lymphatic vessel patterning are not fully elucidated and, to date, no global regulator of lymphatic vessel guidance is known. In this study, we identify the transmembrane cell signalling receptor Plexin D1 (Plxnd1) as a negative regulator of both lymphatic vessel guidance and lymphangiogenesis in zebrafish. plxnd1 is expressed in developing lymphatics and is required for the guidance of both the trunk and facial lymphatic networks. Loss of plxnd1 is associated with misguided intersegmental lymphatic vessel growth and aberrant facial lymphatic branches. Lymphatic guidance in the trunk is mediated, at least in part, by the Plxnd1 ligands, Semaphorin 3AA and Semaphorin 3C. Finally, we show that Plxnd1 normally antagonises Vegfr/Erk signalling to ensure the correct number of facial LECs and that loss of plxnd1 results in facial lymphatic hyperplasia. As a global negative regulator of lymphatic vessel development, the Sema/Plxnd1 signalling pathway is a potential therapeutic target for treating diseases associated with dysregulated lymphatic growth.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-22T17:28:07.86Z","creation":"2025-04-06T02:05:46.117Z"},"accession":"S-EPMC9720674","cross_references":{"pubmed":["36205097"],"doi":["10.1242/dev.200560"]}}