Plexin D1 negatively regulates zebrafish lymphatic development

Britto, DD; He, J; Misa, JP; Chen, W; Kakadia, PM; Grimm, L; Herbert, CD; Crosier, KE; Crosier, PS; Bohlander, SK; Hogan, BM; Hall, CJ; Torres-Vazquez, J; Astin, JW

Author(s): Britto, DD; He, J; Misa, JP; Chen, W; Kakadia, PM; Grimm, L; Herbert, CD; Crosier, KE; Crosier, PS; Bohlander, SK; Hogan, BM; Hall, CJ; Torres-Vazquez, J; Astin, JW;
Details: Publication Year 2022-11-01,Volume 149,Issue #21,Page dev200560
Journal Title: Development
Publication Type: Research article
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.
Keywords: Animals; Zebrafish/genetics/metabolism; Endothelial Cells/metabolism; Nerve Tissue Proteins/genetics/metabolism; Lymphangiogenesis/genetics; *Lymphatic Vessels/metabolism; *Semaphorins/genetics/metabolism; Carrier Proteins/metabolism; Receptors, Cell Surface/genetics/metabolism; Zebrafish Proteins/genetics/metabolism; Lymphangiogenesis; Lymphatic; Plexin D1; Vegfr; Zebrafish
Department(s): Laboratory Research
PubMed ID: 36205097
Publisher's Version: https://doi.org/10.1242/dev.200560
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-11 04:24:42

Last Modified: 2024-10-11 04:26:13