Genomes and Genes
Gene Symbol: hey2
Description: hes-related family bHLH transcription factor with YRPW motif 2
Alias: grl, zgc:136746, hairy/enhancer-of-split related with YRPW motif protein 2, Herp2, gridlock, hairy/enhancer-of-split related with YRPW motif 2, protein gridlock
- 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. ..
- Aranguren X, Beerens M, Vandevelde W, Dewerchin M, Carmeliet P, Luttun A. Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis. Biochem Biophys Res Commun. 2011;410:121-6 pubmed publisher..Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved...
- 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. ..
- Rutenberg J, Fischer A, Jia H, Gessler M, Zhong T, Mercola M. Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy-related transcription factors. Development. 2006;133:4381-90 pubmed..Similarly, zebrafish gridlock (Hey2 homolog) mutant embryos showed ectopic expression of Bmp4, which normally marks AVC myocardium in this ..
- Qian F, Zhen F, Xu J, Huang M, Li W, Wen Z. Distinct functions for different scl isoforms in zebrafish primitive and definitive hematopoiesis. PLoS Biol. 2007;5:e132 pubmed..Our findings suggest that hematopoietic cells at different levels of hierarchy are likely governed by a gradient of the Scl protein established through temporal and spatial patterns of expression of the different isoforms. ..
- Swift M, Pham V, Castranova D, Bell K, Poole R, Weinstein B. SoxF factors and Notch regulate nr2f2 gene expression during venous differentiation in zebrafish. Dev Biol. 2014;390:116-25 pubmed publisher..We show that Notch signaling activity present in the dorsal aorta suppresses expression of nr2f2, restricting nr2f2-dependent promotion of venous differentiation to the cardinal vein. ..
- 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. ..
- Foley J, Yeh J, Maeder M, Reyon D, Sander J, Peterson R, et al. Rapid mutation of endogenous zebrafish genes using zinc finger nucleases made by Oligomerized Pool ENgineering (OPEN). PLoS ONE. 2009;4:e4348 pubmed publisher..engineered ZFN pairs for five endogenous zebrafish genes: tfr2, dopamine transporter, telomerase, hif1aa, and gridlock. Each of these ZFN pairs induces targeted insertions and deletions with high efficiency at its endogenous gene ..
- Sacilotto N, Monteiro R, Fritzsche M, Becker P, Sánchez del Campo L, Liu K, et al. Analysis of Dll4 regulation reveals a combinatorial role for Sox and Notch in arterial development. Proc Natl Acad Sci U S A. 2013;110:11893-8 pubmed publisher..Fascinatingly, this combinatorial ablation leads to a loss of arterial markers and the absence of a detectable dorsal aorta, demonstrating the essential roles of SoxF and Notch, together, in the acquisition of arterial identity. ..
- So J, Kim J, Yoo K, Kim H, Jung S, Choi J, et al. FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development. PLoS ONE. 2014;9:e109517 pubmed publisher..Taken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity. ..
- Hirashima M, Suda T. Differentiation of arterial and venous endothelial cells and vascular morphogenesis. Endothelium. 2006;13:137-45 pubmed..These insights indicate that the balance of these genetic factors and modification by epigenetic factors such as hemodynamics and oxygen tension are important for proper endothelial cell identities in vascular morphogenesis. ..
- Rodriguez F, Vacaru A, Overvoorde J, den Hertog J. The receptor protein-tyrosine phosphatase, Dep1, acts in arterial/venous cell fate decisions in zebrafish development. Dev Biol. 2008;324:122-30 pubmed publisher..were rescued by inhibition of Phosphatidylinositol-3 kinase (PI3K) and by expression of active Notch and Grl/Hey2. Our results suggest a model in which Dep1 acts upstream in a signaling pathway inhibiting PI3K, resulting in ..
- Guiu J, Bergen D, de Pater E, Islam A, AyllÃ³n V, Gama Norton L, et al. Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence. J Exp Med. 2014;211:2411-23 pubmed publisher..Thus, our study identifies Cdca7 as an evolutionary conserved Notch target involved in HSC emergence. ..
- Hogan B, Bussmann J, Wolburg H, Schulte Merker S. ccm1 cell autonomously regulates endothelial cellular morphogenesis and vascular tubulogenesis in zebrafish. Hum Mol Genet. 2008;17:2424-32 pubmed publisher..Finally, we show that ccm1 function is cell autonomous, suggesting that it is endothelial cellular morphogenesis that is regulated by CCM proteins during development and pathogenesis. ..
- Mei J, Liu S, Li Z, Gui J. Mtmr8 is essential for vasculature development in zebrafish embryos. BMC Dev Biol. 2010;10:96 pubmed publisher..Here, we attempt to explore the function of Mtmr8 in vasculature development parallel to its function in muscle development...
- Moore J, Sheppard Tindell S, Shestopalov I, Yamazoe S, Chen J, Lawson N. Post-transcriptional mechanisms contribute to Etv2 repression during vascular development. Dev Biol. 2013;384:128-40 pubmed publisher..Taken together, our results suggest that etv2 acts during early development to specify endothelial lineages and is then down-regulated, in part through post-transcriptional repression by microRNAs, to allow normal vascular development. ..
- He Q, Zhang C, Wang L, Zhang P, Ma D, Lv J, et al. Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates. Blood. 2015;125:1098-106 pubmed publisher..Our findings establish a previously unrecognized link between inflammatory signaling and HSPC emergence, and provide new insights into regenerative medicine and novel therapies to treat innate immune-related diseases. ..
- Olena A, Rao M, Thatcher E, Wu S, Patton J. miR-216a regulates snx5, a novel notch signaling pathway component, during zebrafish retinal development. Dev Biol. 2015;400:72-81 pubmed publisher..We propose a model in which SNX5, precisely controlled by miR-216a, is a vital partner of Mib in promoting endocytosis of Delta and subsequent activation of Notch signaling. ..
- Jin D, Zhu D, Fang Y, Chen Y, Yu G, Pan W, et al. Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures. J Genet Genomics. 2017;44:483-492 pubmed publisher..These findings suggest that Vegfa signaling governs the formation of diverse arteries/veins by distinct cellular mechanisms in vertebrate vasculatures. ..
- Tu X, Deng Y, Chen J, Hu Q, He C, Jordan J, et al. Screening study on the anti-angiogenic effects of Traditional Chinese Medicine - Part I: Heat-clearing and detoxicating TCM. J Ethnopharmacol. 2016;194:280-287 pubmed publisher..The results provide new insights into their clinical application and therapeutic potential for the management of angiogenesis-dependent diseases such as cancer. ..
- Jia H, King I, Chopra S, Wan H, Ni T, Jiang C, et al. Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5. Proc Natl Acad Sci U S A. 2007;104:14008-13 pubmed..Here, we establish Gridlock (Grl), a Hairy-related basic helix-loop-helix (bHLH) transcription factor, as a negative regulator of ..
- Goi M, Childs S. Patterning mechanisms of the sub-intestinal venous plexus in zebrafish. Dev Biol. 2016;409:114-128 pubmed publisher..However Vegf promotes sprouting of the predominantly venous plexus and Bmp promotes outgrowth of the structure. We propose that the SIVP is a unique model to understand novel mechanisms utilized in organ-specific angiogenesis. ..
- Hogan B, Herpers R, Witte M, Helotera H, Alitalo K, Duckers H, et al. Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries. Development. 2009;136:4001-9 pubmed publisher..We propose that this mechanism contributes to the differential response of developing arteries and veins to a constant source of Vegfc present in the embryo during angiogenesis. ..
- Chiang I, Fritzsche M, Pichol Thievend C, Neal A, Holmes K, Lagendijk A, et al. SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development. Development. 2017;144:2629-2639 pubmed publisher..These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates. ..
- Smith K, Lagendijk A, Courtney A, Chen H, Paterson S, Hogan B, et al. Transmembrane protein 2 (Tmem2) is required to regionally restrict atrioventricular canal boundary and endocardial cushion development. Development. 2011;138:4193-8 pubmed publisher..Finally, we show that immature AVC expansion in wkm mutants is rescued by depleting Bmp4, indicating that Tmem2 restricts bmp4 expression to delimit the AVC primordium during cardiac development. ..
- Mouillesseaux K, Chen J. Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos. PLoS ONE. 2011;6:e25013 pubmed publisher..Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos. ..
- Zhou M, Yan J, Ma Z, Zhou Y, Abbood N, Liu J, et al. Comparative and evolutionary analysis of the HES/HEY gene family reveal exon/intron loss and teleost specific duplication events. PLoS ONE. 2012;7:e40649 pubmed publisher..This study shows a model of gene family analysis with gene structure evolution and duplication. ..
- Gajewski M, Voolstra C. Comparative analysis of somitogenesis related genes of the hairy/Enhancer of split class in Fugu and zebrafish. BMC Genomics. 2002;3:21 pubmed..Comparison to the human genome suggests a selective duplication of h/E(spl) genes in pufferfish or loss of members of these genes during evolution to the human lineage. ..
- Peterson R, Shaw S, Peterson T, Milan D, Zhong T, Schreiber S, et al. Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Nat Biotechnol. 2004;22:595-9 pubmed..The zebrafish mutation gridlock (grl, affecting the gene hey2) disrupts aortic blood flow in a region and physiological manner akin to aortic ..
- Liu Y, Guo L. Endothelium is required for the promotion of interrenal morphogenetic movement during early zebrafish development. Dev Biol. 2006;297:44-58 pubmed..We thus conclude that endothelial signaling is involved in the morphogenetic movement of early interrenal tissue. ..
- Hermans K, Claes F, Vandevelde W, Zheng W, Geudens I, Orsenigo F, et al. Role of synectin in lymphatic development in zebrafish and frogs. Blood. 2010;116:3356-66 pubmed publisher..These findings reveal a novel role for synectin in lymphatic development...
- Pendeville H, Winandy M, Manfroid I, Nivelles O, Motte P, Pasque V, et al. Zebrafish Sox7 and Sox18 function together to control arterial-venous identity. Dev Biol. 2008;317:405-16 pubmed publisher..venous Flt4 marker in the dorsal aorta and a concomitant reduction of the artery-specific markers EphrinB2a and Gridlock. The striking similarities between the phenotype of Sox7/Sox18 morphants and Gridlock mutants strongly suggest ..
- Hashiura T, Kimura E, Fujisawa S, Oikawa S, Nonaka S, Kurosaka D, et al. Live imaging of primary ocular vasculature formation in zebrafish. PLoS ONE. 2017;12:e0176456 pubmed publisher..Furthermore, this new morphological information enables us to assess the entire process of the primary ocular vasculature formation, which will be useful for its precise understanding. ..
- Ny A, Autiero M, Carmeliet P. Zebrafish and Xenopus tadpoles: small animal models to study angiogenesis and lymphangiogenesis. Exp Cell Res. 2006;312:684-93 pubmed..The advantages of these two models will be discussed in the present review. ..
- Just S, Berger I, Meder B, Backs J, Keller A, Marquart S, et al. Protein kinase D2 controls cardiac valve formation in zebrafish by regulating histone deacetylase 5 activity. Circulation. 2011;124:324-34 pubmed publisher..Accordingly, the expression of Notch target genes, such as Hey1, Hey2, and HeyL, is severely decreased in bng mutant embryos...
- Chen D, Li L, Tu X, Yin Z, Wang Q. Functional characterization of Klippel-Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis. Hum Mol Genet. 2013;22:963-76 pubmed publisher..We propose that increased AGGF1 expression leads to increased vein differentiation by inducing activation of AKT signaling, resulting in VMs s in KTS patients. ..
- Kartopawiro J, Bower N, Karnezis T, Kazenwadel J, Betterman K, Lesieur E, et al. Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development. Hum Mol Genet. 2014;23:1286-97 pubmed publisher..Our data refine common mechanisms that are likely to contribute during both development and the pathogenesis of lymphatic vascular disorders...
- 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. ..
- Wu B, Chiu C, Chen C, Wang W, Wang J, Wen Z, et al. Nuclear receptor subfamily 2 group F member 1a (nr2f1a) is required for vascular development in zebrafish. PLoS ONE. 2014;9:e105939 pubmed publisher..We further showed that nr2f1a likely interact with Notch signaling by examining nr2f1a expression in rbpsuh morphants and DAPT-treatment embryos. Together, we show nr2f1a plays a critical role for vascular development in zebrafish. ..
- Chen X, Gays D, Milia C, Santoro M. Cilia Control Vascular Mural Cell Recruitment in Vertebrates. Cell Rep. 2017;18:1033-1047 pubmed publisher..In summary, we have identified a hemodynamic-dependent mechanism in the developing vasculature that controls vMC recruitment. ..
- De Angelis J, Lagendijk A, Chen H, Tromp A, Bower N, Tunny K, et al. Tmem2 Regulates Embryonic Vegf Signaling by Controlling Hyaluronic Acid Turnover. Dev Cell. 2017;40:123-136 pubmed publisher..Based on these data, and the known structure of Tmem2, we find that Tmem2 regulates HA turnover to promote normal Vegf signaling during developmental angiogenesis. ..
- Chen I, Wang H, Hsieh Y, Huang W, Yeh H, Chuang Y. PRSS23 is essential for the Snail-dependent endothelial-to-mesenchymal transition during valvulogenesis in zebrafish. Cardiovasc Res. 2013;97:443-53 pubmed publisher..We demonstrated for the first time that the initiation of EndoMT in valvulogenesis depends on PRSS23-Snail signalling and that the functional role of PRSS23 during AV valve formation is evolutionarily conserved. ..
- Hermkens D, van Impel A, Urasaki A, Bussmann J, Duckers H, Schulte Merker S. Sox7 controls arterial specification in conjunction with hey2 and efnb2 function. Development. 2015;142:1695-704 pubmed publisher..An identical circulatory short loop could also be observed in newly generated mutants for hey2 and efnb2...
- Zhang C, Chen Y, Sun B, Wang L, Yang Y, Ma D, et al. m6A modulates haematopoietic stem and progenitor cell specification. Nature. 2017;549:273-276 pubmed publisher..Furthermore, knockdown of Mettl3 in mice confers a similar phenotype. Collectively, our findings demonstrate the critical function of m6A modification in the fate determination of HSPCs during vertebrate embryogenesis. ..
- Shin M, Beane T, Quillien A, Male I, Zhu L, Lawson N. Vegfa signals through ERK to promote angiogenesis, but not artery differentiation. Development. 2016;143:3796-3805 pubmed..Together, these studies implicate ERK as a specific effector of Vegfa signaling in the induction of angiogenic genes during sprouting. ..
- Pouget C, Peterkin T, SimÃµes F, Lee Y, Traver D, Patient R. FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway. Nat Commun. 2014;5:5588 pubmed publisher..These results should help inform strategies to recapitulate the development of HSCs in vitro from pluripotent precursors. ..
- Carney S, Chen J, Burns C, Xiong K, Peterson R, Heideman W. Aryl hydrocarbon receptor activation produces heart-specific transcriptional and toxic responses in developing zebrafish. Mol Pharmacol. 2006;70:549-61 pubmed..More than 70% of the transcripts in this heart-specific cluster promote cellular growth and proliferation. Thus, the developing heart stands out as being responsive to TCDD at both the level of toxicity and gene expression. ..
- Coxam B, Neyt C, Grassini D, Le Guen L, Smith K, Schulte Merker S, et al. carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (cad) regulates Notch signaling and vascular development in zebrafish. Dev Dyn. 2015;244:1-9 pubmed publisher..These findings suggest important posttranslational modifications requiring Cad as an unappreciated mechanism that regulates Notch/Vegf signaling during angiogenesis. ..
- Dyer C, Linker C, Graham A, Knight R. Specification of sensory neurons occurs through diverse developmental programs functioning in the brain and spinal cord. Dev Dyn. 2014;243:1429-39 pubmed publisher..Our work reveals fundamental differences between the development of MTN and RB neurons and suggests that these populations are non-homologous and thus have distinct developmental and, probably, evolutionary origins. ..
- Rost M, Sumanas S. Hyaluronic acid receptor Stabilin-2 regulates Erk phosphorylation and arterial--venous differentiation in zebrafish. PLoS ONE. 2014;9:e88614 pubmed publisher..These results argue that Stab2 is involved in a novel signaling pathway that plays an important role in regulating Erk phosphorylation and establishing arterial-venous identity...
- Wu T, Wang Y, Song Y, Chen Z, Chen Y, Chiu C, et al. Fine-tune regulation of carboxypeptidase N1 controls vascular patterning during zebrafish development. Sci Rep. 2017;7:1852 pubmed publisher..In conclusion, we demonstrate that cpn1 has a critical role in the vascular development of zebrafish. We also reveal a fine-tune regulation of cpn1 that controls vascular patterning mediated by multiple signals. ..
- Packard R, Baek K, Beebe T, Jen N, Ding Y, Shi F, et al. Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair. Sci Rep. 2017;7:8603 pubmed publisher..05, n?=?6-14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy. ..
- Zhao L, Borikova A, Ben Yair R, Guner Ataman B, Macrae C, Lee R, et al. Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Proc Natl Acad Sci U S A. 2014;111:1403-8 pubmed publisher..Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling. ..
- Gupta A, Christensen R, Rayla A, Lakshmanan A, Stormo G, Wolfe S. An optimized two-finger archive for ZFN-mediated gene targeting. Nat Methods. 2012;9:588-90 pubmed publisher..Using this archive, we introduced lesions at 9 of 11 target sites in the zebrafish genome. ..
- Parrie L, Renfrew E, Wal A, Mueller R, Garrity D. Zebrafish tbx5 paralogs demonstrate independent essential requirements in cardiac and pectoral fin development. Dev Dyn. 2013;242:485-502 pubmed publisher..Collectively, these data indicate that, despite similar spatio-temporal expression patterns, tbx5a and tbx5b have independent functions in heart and fin development. ..