Zebrafish mutants in vegfab can affect endothelial cell proliferation without altering ERK phosphorylation and are phenocopied by loss of PI3K signaling

Lange, Martin; Ohnesorge, Nils; Hoffmann, Dennis; Rocha, Susana; Benedito, Rui; Siekmann, Arndt F.

doi:10.1016/j.ydbio.2022.03.006

Cited by 10 publications

(8 citation statements)

References 83 publications

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Section: Discussionmentioning

confidence: 99%

“…In mice, Vegf signaling drives migration of coronary endothelial 43,72 and endocardial endothelial cells 58 in developing hearts, and proliferation of coronary ECs in heart explant cultures 73 . In zebrafish, vegfa mutants show reduced EC proliferation possibly via PI3K signaling 74 . Upon cardiac injury, endocardial Vegfa signaling 1 and Vegfc-mediated (Cxcl8a/Cxcr1-driven) coronary EC proliferation 75 The precise source of Vegf ligand in injured mouse hearts could be the endocardium 76 , myocardium (Vegfa) 58,77 , epicardium (Vegfc 43 , or Vegfa 78 ), or cardiac endothelial cells 75 , thus suggesting an autocrine or paracrine signaling as observed in injured zebrafish hearts 75 .…”

Section: Reactivation Of Developmental Pathways Upon Injury?mentioning

confidence: 99%

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De-differentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development

Arolkar

Sneha

Wang

et al. 2022

Preprint

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Collateral arteries act as natural bypasses, which re-route blood flow to ischemic regions and facilitate tissue regeneration. In the heart, injured neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called Artery Reassembly, aids complete cardiac regeneration in neonatal hearts, but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries, like in cardiomyocytes, is dictated by their ability to de-differentiate. We performed single cell RNA sequencing of coronary endothelial cells and identified differences in molecular profiles of neonatal and adult endothelial cells. Neonates show significant increase in actively cycling artery cells that expressed prominent de-differentiation markers. Using both, in silico pathway analyses and in vivo experiments, we show that cell cycle re-entry of pre-existing artery cells and subsequent collateral artery formation, is dependent on arterial VegfR2. This sub-population of de differentiated and proliferating artery cells is absent in non-regenerative P7 or adult hearts. Together, our data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to de-differentiate and proliferate.

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Section: Discussionmentioning

confidence: 99%

Section: Reactivation Of Developmental Pathways Upon Injury?mentioning

confidence: 99%

De-differentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development

Arolkar

Sneha

Wang

et al. 2022

Preprint

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“…Multiple functions that were prior to the genome duplication executed by a single protein (e.g., VEGF-A) might be executed by two (zebrafish) or even more (Salmonidae, Catostomidae, Cyprinus carpio ) ohnologs. There is multiple evidence that the two zebrafish ohnologs vegfaa and vegfab have diversified in terms of mRNA splicing and, consequently, their angiogenic properties [101, 121, 122]. Similarly, the ohnologs vegfc and vegfd have diversified differently in fishes compared to terrestrial animals in tissue distribution and receptor interaction [123, 124].…”

Section: Discussionmentioning

confidence: 99%

Section: Fish As Model Organismsmentioning

confidence: 99%

Expansion and collapse of VEGF diversity in major clades of the animal kingdom

Rauniyar

Bokharaie

Jeltsch

2022

Preprint

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The vascular endothelial growth factor (VEGF) family comprises in vertebrates five or six members: VEGF(-A), PlGF, VEGF-B, VEGF-C, VEGF-D, and - in venomous reptiles - VEGF-F. They fulfill mainly functions for the blood and lymphatic vascular systems. Together with the platelet-derived growth factors (PDGF-A to -D), they form the PDGF/VEGF subgroup among cystine-knot growth factors. Despite an absent vascular system in most invertebrates, PDGF/VEGF-like molecules have been found in, e.g., Drosophila melanogaster and Caenorhabditis elegans. The evolutionary relationship between PDGF and VEGF growth factors has only been addressed by older analyses, which were limited by the sparse sequencing data at the time. Here we perform a comprehensive analysis of the occurrence of PDGF/VEGF-like growth factors (PVFs) throughout all animal phyla and propose a likely phylogenetic tree. The three major vertebrate whole genome duplications play a role in the expansion of PDGF/VEGF diversity, but several limited duplications are necessary to account for the temporal pattern of emergence. The phylogenetically oldest PVFs likely featured a C-terminus with a BR3P signature, which is a hallmark of the modern-day lymphangiogenic growth factors, VEGF-C and VEGF-D. Some of the younger VEGF genes appeared completely absent in some clades, e.g., functional VEGFB genes in the clade Archosauria, which includes crocodiles, birds, and other dinosaurs, and pgf in amphibians. The lack of precise counterparts for human genes poses limitations, but also offers opportunities for research using organisms that diverge considerably from humans if the goal is to understand human physiology.

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“…Previously described zebrafish lines were Tg(−0 . 8flt1:RFP) hu5333 (Bussmann et al, 2010), TgBAC(pdgfrb:gal4ff) ncv24 (Ando et al, 2016), Tg(TP1bglob:VenusPEST) s940 (Ninov et al, 2012), Tg(TP1bglob:H2B-mCherry) s939 (Ninov et al ., 2012), Tg3(fli1:LIFEACT-EGFP) mu240 (Hamm et al, 2016), Tg(fli1a:nEGFP) Y7 (Roman et al, 2002), Tg(gata1:dsRed) sd2 (Traver et al, 2003), TgBAC(cxcr4a:YFP) mu104 (Xu et al ., 2014), Tg (flt4:citrine) hu7135 (van Impel et al, 2014), Tg(kdrl:EGFP) s843 (Jin et al, 2005), kdrl hu5088 (Bussmann et al ., 2010), vegfaa mu128 (Lange et al, 2022). Some of the transgenic lines were kept in a casper ( roy, nacre ) double mutant background (White et al, 2008) to increase clarity for imaging due to loss of pigment cells.…”

Section: Methodsmentioning

confidence: 99%

Temporally and regionally distinct morphogenetic processes govern zebrafish tail fin blood vessel network expansion

Leonard

Hasan

Siekmann

2022

Preprint

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Blood vessels form elaborate networks depending on tissue-specific signalling pathways and anatomical structures to guide their growth. However, it is not clear which morphogenetic principles organize the stepwise assembly of the vasculature. We thus performed a longitudinal analysis of zebrafish tail fin vascular assembly, revealing the existence of temporally and spatially distinct morphogenetic processes. Initially, vein-derived endothelial cells (ECs) generated arteries in a reiterative process requiring Vascular Endothelial Growth Factor (VEGF), Notch and cxcr4a signalling. Subsequently, veins produced veins in more proximal fin regions, transforming pre-existing artery-vein loops into a three-vessel pattern consisting of an artery and two veins. A distinct set of vascular plexuses formed at the base of the fin. They differed by virtue of diameter, flow magnitude and marker gene expression. At later stages, intussusceptive angiogenesis occurred from veins in distal fin regions. In proximal fin regions, we observed new vein sprouts crossing the inter-ray tissue through sprouting angiogenesis. Together, our results reveal a surprising diversity among the mechanisms generating the mature fin vasculature and suggest that these might be driven by separate local cues.

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Zebrafish mutants in vegfab can affect endothelial cell proliferation without altering ERK phosphorylation and are phenocopied by loss of PI3K signaling

Cited by 10 publications

References 83 publications

De-differentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development

De-differentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development

Expansion and collapse of VEGF diversity in major clades of the animal kingdom

Temporally and regionally distinct morphogenetic processes govern zebrafish tail fin blood vessel network expansion

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