PUBLICATION
Plexind1 negatively regulates zebrafish lymphatic development
- Authors
- Britto, D.D., He, J., Misa, J.P., Chen, W., Kakadia, P.M., Grimm, L., Herbert, C.D., Crosier, K.E., Crosier, P.S., Bohlander, S.K., Hogan, B.M., Hall, C.J., Torres-Vázquez, J., Astin, J.W.
- ID
- ZDB-PUB-221008-3
- Date
- 2022
- Source
- Development (Cambridge, England) 149(21): (Journal)
- Registered Authors
- Astin, Jonathan, Chen, Wenxuan, Crosier, Kathy, Crosier, Phil, Herbert, Caitlin, Hogan, Ben M.
- Keywords
- Guidance, Lymphangiogenesis, Lymphatic, Plexind1, Zebrafish
- MeSH Terms
-
- Animals
- Carrier Proteins/metabolism
- Endothelial Cells/metabolism
- Lymphangiogenesis/genetics
- Lymphatic Vessels*/metabolism
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/metabolism
- Semaphorins*/genetics
- Semaphorins*/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36205097 Full text @ Development
Citation
Britto, D.D., He, J., Misa, J.P., Chen, W., Kakadia, P.M., Grimm, L., Herbert, C.D., Crosier, K.E., Crosier, P.S., Bohlander, S.K., Hogan, B.M., Hall, C.J., Torres-Vázquez, J., Astin, J.W. (2022) Plexind1 negatively regulates zebrafish lymphatic development. Development (Cambridge, England). 149(21).
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 Plexind1 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, Semaphorin3aa and Semaphorin3c. 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 to treat diseases associated with dysregulated lymphatic growth.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping