PT  - JOURNAL ARTICLE
AU  - Koji Ando
AU  - Yu-Huan Shih
AU  - Lwaki Ebarasi
AU  - Ann Grosse
AU  - Daneal Portman
AU  - Ayano Chiba
AU  - Kenny Mattonet
AU  - Claudia Gerri
AU  - Didier Y.R. Stainier
AU  - Naoki Mochizuki
AU  - Shigetomo Fukuhara
AU  - Christer Betsholtz
AU  - Nathan D. Lawson
TI  - Conserved and context-dependent roles for Pdgfrb signaling during zebrafish vascular mural cell development
AID  - 10.1101/2021.03.29.437552
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.29.437552
4099  - http://biorxiv.org/content/early/2021/03/29/2021.03.29.437552.short
4100  - http://biorxiv.org/content/early/2021/03/29/2021.03.29.437552.full
AB  - 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. 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 mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects.Summary statement Genetic analysis in zebrafish demonstrates the conserved role of Pdgfb/Pdgfrb signaling in pericyte and vascular smooth muscle cell formation during vascular development in vertebrates.Competing Interest StatementThe authors have declared no competing interest.