Zebrafish Vascular Mural Cell Biology: Recent Advances, Development, and Functions

Abstract

Recruitment of mural cells to the vascular wall is essential for forming the vasculature as well as maintaining proper vascular functions. In recent years, zebrafish genetic tools for mural cell biology have improved substantially. Fluorescently labeled zebrafish mural cell reporter lines enable us to study, with higher spatiotemporal resolution than ever, the processes of mural cell development from their progenitors. Furthermore, recent phenotypic analysis of platelet-derived growth factor beta mutant zebrafish revealed well-conserved organotypic mural cell development and functions in vertebrates with the unique features of zebrafish. However, comprehensive reviews of zebrafish mural cells are lacking. Therefore, herein, we highlight recent advances in zebrafish mural cell tools. We also summarize the fundamental features of zebrafish mural cell development, especially at early stages, and functions.

Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells

“…The pdgfrb:egfp cells used in Shih et al were from whole embryos, and the pericytes noted above were therefore not necessarily associated with trunk blood vessels ( Shih et al, 2021 ). Therefore, we determined expression of vegfc, ccbe1, and cxcl12a in (MC-enriched) EGFP-positive cells isolated from micro-dissected trunks of TgBAC(abcc9:Gal4FF);Tg(UAS:EGFP ) larvae at 3 dpf, in comparison to negative cells ( Figure 3D–E , Figure 3—figure supplement 3C ; Ando et al, 2021 ). To assess the expression level of these genes in arteries, we also sorted aECs from micro-dissected trunks of Tg(flt1;YFP ) line ( Figure 3D–E , Figure 3—figure supplement 3C ).…”

Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration

“…2c) 30,31 . Further analysis of the mural cells demonstrated enriched transcripts for known pericyte and vascular smooth muscle cell markers, including tropomyosin 1 (tpm1), notch receptor 3 (notch3), regulator of G protein signaling 5a (rgs5a), myosin heavy chain 11a (myh11a), actin alpha 2 smooth muscle (acta2), transgelin (tagln), ATP-binding cassette sub-family C member 9 (abcc9), and chemokine C-X-C motif ligand 12b (cxcl12b), as well as two recently identified mural cell markers NDUFA4 mitochondrial complex associated like 2a (ndufa4l2a) and potassium voltage-gated channel Iskrelated family member 4 (kcne4) 32,33 (Supplementary Fig. 2c).…”

Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration

“…Besides these contaminating clusters, cluster 6 was identified as mural cells expressing platelet-derived growth factor receptor beta pdgfrb (Figure 2C) 29, 30 . Further analysis of the mural cells demonstrated enriched transcripts for known pericyte and vascular smooth muscle cell markers, including tropomyosin 1 ( tpm1 ), notch receptor 3 ( notch3 ), regulator of G protein signaling 5a ( rgs5a ), myosin heavy chain 11a ( myh11a ), actin alpha 2 smooth muscle ( acta2 ), transgelin ( tagln ), ATP-binding cassette sub-family C member 9 ( abcc9 ), and chemokine C-X-C motif ligand 12b ( cxcl12b ), as well as two recently identified mural cell markers NDUFA4 mitochondrial complex associated like 2a ( ndufa4l2a ) and potassium voltage-gated channel Isk-related family member 4 ( kcne4 ) 31, 32 (Figure S2C). While ndufa4l2a is restricted to a subset of mural cells, kcne4 is highly expressed in mural cells and also present in the core epicardial clusters at lower levels.…”