Genomes and Genes
Gene Symbol: kdrl
Description: kinase insert domain receptor like
Alias: flk, flk-1, flk1, kdr, kdra, vegfr-2, vegfr2, vegfr2a, vegfr4, vegr2, wu:fk52c05, vascular endothelial growth factor receptor kdr-like, VEGFR-4, fetal liver kinase 1, flt1b, kinase insert domain receptor-A, protein-tyrosine kinase receptor flk-1, vascular endothelial growth factor receptor 2, vascular endothelial growth factor receptor 4, vascular endothelial growth factor receptor type 2
- Lawson N, Mugford J, Diamond B, Weinstein B. phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development. Genes Dev. 2003;17:1346-51 pubmed..Our results indicate that Plcg1 functions specifically downstream of the Vegf receptor during embryonic development to govern formation of the arterial system. ..
- Krueger J, Liu D, Scholz K, Zimmer A, Shi Y, Klein C, et al. Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo. Development. 2011;138:2111-20 pubmed publisher..Zebrafish embryos expressed soluble Flt1 (sFlt1) and membrane-bound Flt1 (mFlt1). In Tg(flt1(BAC):yfp) × Tg(kdrl:ras-cherry)(s916) embryos, flt1:yfp was expressed in tip, stalk and base cells of segmental artery sprouts and ..
- Choi J, Dong L, Ahn J, Dao D, Hammerschmidt M, Chen J. FoxH1 negatively modulates flk1 gene expression and vascular formation in zebrafish. Dev Biol. 2007;304:735-44 pubmedb>Flk1 is the major receptor for VEGF on endothelial cells. During embryogenesis, flk1 is required for both vasculogenesis and angiogenesis and abnormally elevated flk1 expression is often associated with pathological conditions in adults...
- Nicoli S, Ribatti D, Cotelli F, Presta M. Mammalian tumor xenografts induce neovascularization in zebrafish embryos. Cancer Res. 2007;67:2927-31 pubmed..and express the transcripts for the zebrafish orthologues of the early endothelial markers Fli-1, VEGF receptor-2 (VEGFR2/KDR), and VE-cadherin...
- Lenard A, Ellertsdottir E, Herwig L, Krudewig A, Sauteur L, Belting H, et al. In vivo analysis reveals a highly stereotypic morphogenetic pathway of vascular anastomosis. Dev Cell. 2013;25:492-506 pubmed publisher..Vascular endothelial-cadherin plays an important role early in the anastomosis process and is required for filopodial tip cell interactions and efficient formation of a single contact site. ..
- Jin S, Herzog W, Santoro M, Mitchell T, Frantsve J, Jungblut B, et al. A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Dev Biol. 2007;307:29-42 pubmed..All putative mutants were then crossed into the Tg(flk1:EGFP)(s843) transgenic background to facilitate detailed examination of endothelial cells in live and fixed embryos...
- Fouquet B, Weinstein B, Serluca F, Fishman M. Vessel patterning in the embryo of the zebrafish: guidance by notochord. Dev Biol. 1997;183:37-48 pubmedWe have cloned the zebrafish homolog of the receptor tyrosine kinase flk-1 to provide us with a tool to study normal vascular pattern formation in the developing zebrafish embryo and to compare it to mutants in which vascular pattern is ..
- Murphy E, Shields D, Stoletov K, Dneprovskaia E, McElroy M, Greenberg J, et al. Disruption of angiogenesis and tumor growth with an orally active drug that stabilizes the inactive state of PDGFRbeta/B-RAF. Proc Natl Acad Sci U S A. 2010;107:4299-304 pubmed publisher..Our lead compound was selected as an orally active molecule with favorable pharmacokinetic properties which demonstrated target inhibition in vivo leading to suppression of murine orthotopic tumors in both the kidney and pancreas. ..
- Bertrand J, Chi N, Santoso B, Teng S, Stainier D, Traver D. Haematopoietic stem cells derive directly from aortic endothelium during development. Nature. 2010;464:108-11 pubmed publisher..Finally, using a permanent lineage tracing strategy, we demonstrate that the HSCs generated from haemogenic endothelium are the lineal founders of the adult haematopoietic system. ..
- Xiong J, Yu Q, Zhang J, Mably J. An acyltransferase controls the generation of hematopoietic and endothelial lineages in zebrafish. Circ Res. 2008;102:1057-64 pubmed publisher..Epistasis analysis supports that lycat acts upstream of scl and etsrp in zebrafish hemangioblast development. These data indicate that lycat is the earliest known player in the generation of both endothelial and hematopoietic lineages. ..
- Herbert S, Huisken J, Kim T, Feldman M, Houseman B, Wang R, et al. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science. 2009;326:294-8 pubmed publisher..Thus, directional control of progenitor migration drives arterial-venous segregation and generation of separate parallel vessels from a single precursor vessel, a process essential for vascular development. ..
- North T, Goessling W, Peeters M, Li P, Ceol C, Lord A, et al. Hematopoietic stem cell development is dependent on blood flow. Cell. 2009;137:736-48 pubmed publisher..This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development. ..
- Gering M, Rodaway A, Gottgens B, Patient R, Green A. The SCL gene specifies haemangioblast development from early mesoderm. EMBO J. 1998;17:4029-45 pubmed..Our data also underline the striking similarities between the role of SCL in haematopoiesis/vasculogenesis and the function of other bHLH proteins in muscle and neural development. ..
- Siekmann A, Standley C, Fogarty K, Wolfe S, Lawson N. Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev. 2009;23:2272-7 pubmed publisher..These studies reveal unexpected endothelial diversity within the aorta that is necessary to facilitate its regional patterning by local cues. ..
- Latimer A, Appel B. Notch signaling regulates midline cell specification and proliferation in zebrafish. Dev Biol. 2006;298:392-402 pubmed..Together, our results indicate that Notch signaling regulates allocation of appropriate numbers of different midline cells by different mechanisms. ..
- Lam I, Alex D, Wang Y, Liu P, Liu A, Du G, et al. In vitro and in vivo structure and activity relationship analysis of polymethoxylated flavonoids: identifying sinensetin as a novel antiangiogenesis agent. Mol Nutr Food Res. 2012;56:945-56 pubmed publisher..arrest in the G0/G1 phase in HUVEC culture and downregulating the mRNA expressions of angiogenesis genes flt1, kdrl, and hras in zebrafish...
- Gering M, Yamada Y, Rabbitts T, Patient R. Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which differentiate into endothelial cells in the absence of Gata1. Development. 2003;130:6187-99 pubmed..These results suggest that, in the absence of inducers of erythroid or myeloid haematopoiesis, Scl/Tal1-Lmo2-induced haemangioblasts differentiate into endothelial cells. ..
- Rottbauer W, Just S, Wessels G, Trano N, Most P, Katus H, et al. VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart. Genes Dev. 2005;19:1624-34 pubmed..Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility. ..
- Thompson M, Ransom D, Pratt S, MacLennan H, Kieran M, Detrich H, et al. The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis. Dev Biol. 1998;197:248-69 pubmed..The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have been cloned and characterized in this study...
- Kohli V, Schumacher J, Desai S, Rehn K, Sumanas S. Arterial and venous progenitors of the major axial vessels originate at distinct locations. Dev Cell. 2013;25:196-206 pubmed publisher..We propose a revised model of arterial-venous differentiation that explains how angioblasts choose between an arterial and venous fate. ..
- Zygmunt T, Gay C, Blondelle J, Singh M, Flaherty K, Means P, et al. Semaphorin-PlexinD1 signaling limits angiogenic potential via the VEGF decoy receptor sFlt1. Dev Cell. 2011;21:301-14 pubmed publisher..Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance. ..
- Lazic S, Scott I. Mef2cb regulates late myocardial cell addition from a second heart field-like population of progenitors in zebrafish. Dev Biol. 2011;354:123-33 pubmed publisher..Further, as congenital heart disease is often associated with defects in second heart field development, the embryological and genetic advantages of the zebrafish model can be applied to study the vertebrate second heart field. ..
- Hinits Y, Pan L, Walker C, Dowd J, Moens C, Hughes S. Zebrafish Mef2ca and Mef2cb are essential for both first and second heart field cardiomyocyte differentiation. Dev Biol. 2012;369:199-210 pubmed publisher..Mef2cb single mutants have a functional heart and are viable adults. Our results show that the key role of Mef2c in myocardial differentiation is conserved throughout the vertebrate heart. ..
- Zhu C, Smith T, MCNULTY J, Rayla A, Lakshmanan A, Siekmann A, et al. Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish. Development. 2011;138:4555-64 pubmed publisher..This work provides a resource to allow targeted germline gene inactivation in zebrafish and highlights the benefit of a definitive reverse genetic strategy to reveal gene function. ..
- Gering M, Patient R. Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell. 2005;8:389-400 pubmed..Furthermore, HSC and DA formation also share Vegf and Notch requirements, which further distinguishes them from primitive hematopoiesis and underlines their close relationship during vertebrate development. ..
- Jing C, Chen Y, Dong M, Peng X, Jia X, Gao L, et al. Phospholipase C gamma-1 is required for granulocyte maturation in zebrafish. Dev Biol. 2013;374:24-31 pubmed publisher..These results suggested that plcg1 functioned specifically in zebrafish ICM granulopoiesis for the first time. Our studies suggest that specific pathways regulate the differentiation of the hematopoietic lineages. ..
- Nicoli S, De Sena G, Presta M. Fibroblast growth factor 2-induced angiogenesis in zebrafish: the zebrafish yolk membrane (ZFYM) angiogenesis assay. J Cell Mol Med. 2009;13:2061-8 pubmed publisher..are formed by proliferating cells that incorporate bromodeoxyuridine and express the endothelial cell markers vegfr2/kdr and fli1...
- Burns C, Traver D, Mayhall E, Shepard J, Zon L. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev. 2005;19:2331-42 pubmed..These data define the Notch-Runx pathway as critical for the developmental specification of HSC fate and the subsequent homeostasis of HSC number, thus providing a mechanism for amplifying stem cells in vivo...
- Liao W, Ho C, Yan Y, Postlethwait J, Stainier D. Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish. Development. 2000;127:4303-13 pubmed..leads to the premature and ectopic expression of early endothelial and blood differentiation genes such as fli1, flk1 and gata1, indicating that Hhex can positively regulate endothelial and blood differentiation...
- Avraham Davidi I, Ely Y, Pham V, Castranova D, Grunspan M, Malkinson G, et al. ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nat Med. 2012;18:967-73 pubmed publisher..These findings may open new avenues for the treatment of lipoprotein-related vascular disorders. ..
- Ishitobi H, Wakamatsu A, Liu F, Azami T, Hamada M, Matsumoto K, et al. Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse. Development. 2011;138:5357-68 pubmed publisherThe mouse Flk1 gene is expressed in various mesodermal progenitor cells of developing embryos...
- Herbomel P, Thisse B, Thisse C. Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development. 1999;126:3735-45 pubmed
- Chen E, Hermanson S, Ekker S. Syndecan-2 is essential for angiogenic sprouting during zebrafish development. Blood. 2004;103:1710-9 pubmed..Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the development of angiogenesis-based therapies. ..
- Dooley K, Davidson A, Zon L. Zebrafish scl functions independently in hematopoietic and endothelial development. Dev Biol. 2005;277:522-36 pubmed..Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development. ..
- Bahary N, Goishi K, Stuckenholz C, Weber G, Leblanc J, Schafer C, et al. Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish. Blood. 2007;110:3627-36 pubmed..Both VegfAa and VegfAb can individually bind and promote phosphorylation of both Flk1 (Kdra) and Kdrb proteins in vitro...
- Yoo K, Kim E, Jung S, Rhee M, Koo B, Yoon K, et al. Snx5, as a Mind bomb-binding protein, is expressed in hematopoietic and endothelial precursor cells in zebrafish. FEBS Lett. 2006;580:4409-16 pubmed..Taken together, we show that Snx5, a novel interacting partner of Mind bomb, may have an essential role for cell fate determination in early development. ..
- Tang J, Li S, Li Z, Zhang Z, Hu G, Cheang L, et al. Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC. PLoS ONE. 2010;5:e11822 pubmed publisher..vitro and zebrafish embryos in vivo via the up-regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA expression...
- Liu F, Walmsley M, Rodaway A, Patient R. Fli1 acts at the top of the transcriptional network driving blood and endothelial development. Curr Biol. 2008;18:1234-40 pubmed publisher..of Fli1 is sufficient to induce expression of key hemangioblast genes, such as Scl/Tal1, Lmo2, Gata2, Etsrp, and Flk1. Epistasis assays show that Fli1 expression is induced by Bmp signaling or Cloche, depending on the hemangioblast ..
- Liang D, Chang J, Chin A, Smith A, Kelly C, Weinberg E, et al. The role of vascular endothelial growth factor (VEGF) in vasculogenesis, angiogenesis, and hematopoiesis in zebrafish development. Mech Dev. 2001;108:29-43 pubmed..Simultaneous overexpression of both isoforms in the embryo results in increased production of flk1, tie1, scl, and gata1 transcripts, indicating a stimulation of both endothelial and hematopoietic lineages...
- Li X, Lan Y, Xu J, Zhang W, Wen Z. SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish. Development. 2012;139:4321-9 pubmed publisher..Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal hematopoiesis in zebrafish. ..
- Sumanas S, Lin S. Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLoS Biol. 2006;4:e10 pubmed..These results demonstrate that Etsrp is necessary and sufficient for the initiation of vasculogenesis. ..
- Li S, Lou S, Lei B, Chan T, Kwan Y, Chan S, et al. Transcriptional profiling of angiogenesis activities of calycosin in zebrafish. Mol Biosyst. 2011;7:3112-21 pubmed publisher..The data have elucidated the connection between morphological observations and genomic evidence, indicating the potential roles of several key signaling pathways in angiogenesis. ..
- Sumoy L, Keasey J, Dittman T, Kimelman D. A role for notochord in axial vascular development revealed by analysis of phenotype and the expression of VEGR-2 in zebrafish flh and ntl mutant embryos. Mech Dev. 1997;63:15-27 pubmed..Differences in the vascular phenotype between the two mutations correlated with the severity of their axial mesodermal defects. These observations support a role for the notochord in vasculogenesis. ..
- Jin S, Beis D, Mitchell T, Chen J, Stainier D. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development. 2005;132:5199-209 pubmed..To facilitate these studies, we generated a transgenic line where EGFP expression is controlled by the zebrafish flk1 promoter. We find that angioblasts migrate as individual cells to form a vascular cord at the midline...
- van Rooijen E, Voest E, Logister I, Bussmann J, Korving J, van Eeden F, et al. von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish. Dis Model Mech. 2010;3:343-53 pubmed publisher..increased expression of the duplicated VEGFA orthologs vegfaa and vegfab, and of vegfb and its receptors flt1, kdr and kdr-like, indicating increased vascular endothelial growth factor (Vegf) signaling in vhl mutants...
- Wong K, Rehn K, Palencia Desai S, Kohli V, Hunter W, Uhl J, et al. Hedgehog signaling is required for differentiation of endocardial progenitors in zebrafish. Dev Biol. 2012;361:377-91 pubmed publisher..Our results argue that Hh provides a critical signal to induce the specification and differentiation of endocardial progenitors. ..
- Nicoli S, Knyphausen C, Zhu L, Lakshmanan A, Lawson N. miR-221 is required for endothelial tip cell behaviors during vascular development. Dev Cell. 2012;22:418-29 pubmed publisher..These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis. ..
- So J, Hong S, Kim H, Jung S, Lee M, Choi J, et al. Gicerin/Cd146 is involved in zebrafish cardiovascular development and tumor angiogenesis. Genes Cells. 2010;15:1099-110 pubmed publisher..Thus, knock-down of gicerin might have an important implication in controlling tumor angiogenesis. ..
- Covassin L, Siekmann A, Kacergis M, Laver E, Moore J, Villefranc J, et al. A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Dev Biol. 2009;329:212-26 pubmed publisher..with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development...
- Cermenati S, Moleri S, Cimbro S, Corti P, Del Giacco L, Amodeo R, et al. Sox18 and Sox7 play redundant roles in vascular development. Blood. 2008;111:2657-66 pubmed..Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT. ..
- Hao J, Ho J, Lewis J, Karim K, Daniels R, Gentry P, et al. In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol. 2010;5:245-53 pubmed publisher..significant "off-target" effects against the VEGF (vascular endothelial growth factor) type-2 receptor (Flk1/KDR) and disrupts zebrafish angiogenesis...
- Proulx K, Lu A, Sumanas S. Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis. Dev Biol. 2010;348:34-46 pubmed publisher..Such angioblast cluster-derived angiogenesis is likely to be involved during vasculature formation in other vertebrate systems as well. ..
- Kalev Zylinska M, Horsfield J, Flores M, Postlethwait J, Vitas M, Baas A, et al. Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis. Development. 2002;129:2015-30 pubmed..The phenotype obtained with transient expression of RUNX1-CBF2T1 validates the zebrafish as a model system to study t(8;21)-mediated leukemogenesis. ..
- Lawson N, Vogel A, Weinstein B. sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell. 2002;3:127-36 pubmed..These studies reveal a complex signaling cascade responsible for establishing arterial cell fate and suggest differential effects of Vegf on developing endothelial cells. ..
- Rowlinson J, Gering M. Hey2 acts upstream of Notch in hematopoietic stem cell specification in zebrafish embryos. Blood. 2010;116:2046-56 pubmed publisher..These results establish an essential role for Hey2 upstream of Notch in HSC formation. ..
- Nasevicius A, Larson J, Ekker S. Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant. Yeast. 2000;17:294-301 pubmed..Molecular analysis using the endothelial markers fli-1 and flk-1 at 1 day of development demonstrates a fundamental distinction between VEGF-A requirements for axial and ..
- Beis D, Bartman T, Jin S, Scott I, D Amico L, Ober E, et al. Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development. 2005;132:4193-204 pubmed..This collection of mutants provides a unique set of tools to further our understanding of the genetic basis of cell behavior and differentiation during AV valve development. ..
- Lam E, Hall C, Crosier P, Crosier K, Flores M. Live imaging of Runx1 expression in the dorsal aorta tracks the emergence of blood progenitors from endothelial cells. Blood. 2010;116:909-14 pubmed publisher..This study captures the earliest events of the transition of endothelial cells to a hemogenic endothelium and demonstrates that embryonic hematopoietic progenitors directly differentiate from endothelial cells within a living organism. ..
- Williams C, Kim S, Ni T, Mitchell L, Ro H, Penn J, et al. Hedgehog signaling induces arterial endothelial cell formation by repressing venous cell fate. Dev Biol. 2010;341:196-204 pubmed publisher..Collectively, these studies suggest that arterial endothelial cells are specified and formed via repressing venous cell fate at the lateral plate mesoderm by Hh signaling during vasculogenesis. ..
- Pham V, Lawson N, Mugford J, Dye L, Castranova D, Lo B, et al. Combinatorial function of ETS transcription factors in the developing vasculature. Dev Biol. 2007;303:772-83 pubmed..Our results demonstrate that combinatorial ETS factor function is essential for early endothelial specification and differentiation. ..
- Zhong T, Childs S, Leu J, Fishman M. Gridlock signalling pathway fashions the first embryonic artery. Nature. 2001;414:216-20 pubmed..Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision. ..
- Bayliss P, Bellavance K, Whitehead G, Abrams J, Aegerter S, Robbins H, et al. Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish. Nat Chem Biol. 2006;2:265-73 pubmed..This study illustrates the utility of the adult zebrafish as a new model system for receptor signaling and chemical biology. ..
- Habeck H, Odenthal J, Walderich B, Maischein H, Schulte Merker S. Analysis of a zebrafish VEGF receptor mutant reveals specific disruption of angiogenesis. Curr Biol. 2002;12:1405-12 pubmed..Targeted disruption of vascular endothelial growth factor (VEGF) or its receptor kdr (flk1, VEGFR2) in mouse embryos results in a severe reduction of all blood vessels, while the complete loss of flt1 (VEGFR1) ..
- Parker L, Schmidt M, Jin S, Gray A, Beis D, Pham T, et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature. 2004;428:754-8 pubmed..This process fails to take place in Egfl7 knockdown embryos, leading to the failure of vascular tube formation. Our study defines a regulator that controls a specific and important step in vasculogenesis. ..
- Chi N, Shaw R, De Val S, Kang G, Jan L, Black B, et al. Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes Dev. 2008;22:734-9 pubmed publisher..sli/foxn4 is expressed in the AV canal, and its encoded product binds to a highly conserved tbx2 enhancer domain that contains Foxn4- and T-box-binding sites, both necessary to regulate tbx2b expression in the AV canal. ..
- Ober E, Olofsson B, Makinen T, Jin S, Shoji W, Koh G, et al. Vegfc is required for vascular development and endoderm morphogenesis in zebrafish. EMBO Rep. 2004;5:78-84 pubmed