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The RAS Guanyl Nucleotide-releasing Protein RasGRP1 Is Involved in Lymphatic Development in Zebrafish
- Source :
- Journal of Biological Chemistry. 288:2355-2364
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- The molecular basis of the lymphatic development remains largely unknown. Using zebrafish as a model, we discovered a novel role for the Ras guanine-releasing protein 1 (RasGRP1), a protein involved in Ras activation in lymphangiogenesis. Secondary lymphatic sprouts from the posterior cardinal vein give rise to thoracic duct which is the first lymphatic vessel in zebrafish. Knockdown of rasgrp1 by injecting morpholino in zebrafish embryos impaired formation of thoracic duct accompanied by pericardial and truck edema, whereas blood vessel development of the embryos was largely unaffected. In rasgrp1-knockdown embryos, the number of sprouts producing the string of parachordal lymphangioblast cells was reduced. Meanwhile the total number of the secondary sprouts was not changed. As a result, the number of venous intersegmental vessels was increased, whereas the number of lymphatic vessel was reduced at a later stage. The lymphatic developmental defects caused by rasgrp1 knockdown could be rescued by ectopic expression of a constitutively active HRas. Further analysis revealed that RasGRP1 knockdown could synergize with flt4/vegfr3 knockdown to induce defects in lymphangiogenesis. Taken together, this finding demonstrates a critical role for RasGRP1 in lymphatic development in zebrafish.
- Subjects :
- Vascular Endothelial Growth Factor A
Time Factors
animal structures
Morpholino
Green Fluorescent Proteins
Neovascularization, Physiologic
Biochemistry
Thoracic duct
Thoracic Duct
Animals, Genetically Modified
Lymphatic System
medicine
Lymphatic vessel
Animals
Guanine Nucleotide Exchange Factors
Lymphangiogenesis
Molecular Biology
Zebrafish
In Situ Hybridization
Lymphatic Vessels
Gene knockdown
biology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Cell Biology
biology.organism_classification
Molecular biology
Cell biology
DNA-Binding Proteins
medicine.anatomical_structure
Lymphatic system
Vascular endothelial growth factor C
embryonic structures
ras Proteins
Developmental Biology
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 288
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....31827a0ef1d7a91fe04a60b9573a5968