Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development
- Ando, K., Shih, Y.H., Ebarasi, L., Grosse, A., Portman, D., Chiba, A., Mattonet, K., Gerri, C., Stainier, D.Y.R., Mochizuki, N., Fukuhara, S., Betsholtz, C., Lawson, N.D.
- Developmental Biology 479: 11-22 (Journal)
- Registered Authors
- Betsholtz, Christer, Ebarasi, Lwaki, Lawson, Nathan, Mochizuki, Naoki, Stainier, Didier
- Mural cells, Pdgfrb, Pericytes, Vascular smooth muscle cells, Zebrafish
- MeSH Terms
- Cell Differentiation
- Coronary Vessels/metabolism
- Embryonic Development
- Muscle, Smooth, Vascular/embryology
- Muscle, Smooth, Vascular/metabolism*
- Myocytes, Smooth Muscle/metabolism
- Proto-Oncogene Proteins c-sis/metabolism
- Proto-Oncogene Proteins c-sis/physiology
- Receptor, Platelet-Derived Growth Factor beta/genetics
- Receptor, Platelet-Derived Growth Factor beta/metabolism*
- Signal Transduction/genetics
- Zebrafish Proteins/metabolism
- 34310924 Full text @ Dev. Biol.
Ando, K., Shih, Y.H., Ebarasi, L., Grosse, A., Portman, D., Chiba, A., Mattonet, K., Gerri, C., Stainier, D.Y.R., Mochizuki, N., Fukuhara, S., Betsholtz, C., Lawson, N.D. (2021) Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development. Developmental Biology. 479:11-22.
Platelet derived growth factor beta and its receptor, Pdgfrb, play essential roles in the development of vascular mural cells, including pericytes and vascular smooth muscle cells. To determine if this role was conserved in zebrafish, we analyzed pdgfb and pdgfrb mutant lines. Similar to mouse, pdgfb and pdgfrb mutant zebrafish lack brain pericytes and exhibit anatomically selective loss of vascular smooth muscle coverage. Despite these defects, pdgfrb mutant zebrafish did not otherwise exhibit circulatory defects at larval stages. However, beginning at juvenile stages, we observed severe cranial hemorrhage and vessel dilation associated with loss of pericytes and vascular smooth muscle cells in pdgfrb mutants. Similar to mouse, pdgfrb mutant zebrafish also displayed structural defects in the glomerulus, but normal development of hepatic stellate cells. We also noted defective mural cell investment on coronary vessels with concomitant defects in their development. Together, our studies support a conserved requirement for Pdgfrb signaling in mural cells. In addition, these zebrafish mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes