Genomes and Genes
Gene Symbol: hhex
Description: hematopoietically expressed homeobox
Alias: hex, hematopoietically-expressed homeobox protein hhex, homeobox protein hex
- Tehrani Z, Lin S. Antagonistic interactions of hedgehog, Bmp and retinoic acid signals control zebrafish endocrine pancreas development. Development. 2011;138:631-40 pubmed publisher..These results identify multiple sequential roles for Hh in pancreas development and highlight an unexpected antagonistic relationship between Hh and other signaling pathways to control pancreatic specification and differentiation. ..
- 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..Here we report that in zebrafish the homeobox gene hhex (previously called hex) is also expressed in endothelial and blood lineages from an early stage...
- Shin D, Weidinger G, Moon R, Stainier D. Intrinsic and extrinsic modifiers of the regulative capacity of the developing liver. Mech Dev. 2012;128:525-35 pubmed publisher..Altogether, these studies reveal that there is more than one way to form a liver, and provide molecular insights into the phenomenon of tissue plasticity. ..
- Kinkel M, Sefton E, Kikuchi Y, Mizoguchi T, Ward A, Prince V. Cyp26 enzymes function in endoderm to regulate pancreatic field size. Proc Natl Acad Sci U S A. 2009;106:7864-9 pubmed publisher..Such feedback can maintain consistent levels of RA signaling, despite environmental fluctuations in RA concentration, thus ensuring a consistent size and location of the pancreatic field. ..
- Ober E, Verkade H, Field H, Stainier D. Mesodermal Wnt2b signalling positively regulates liver specification. Nature. 2006;442:688-91 pubmed..In zebrafish, the onset of liver specification is marked by the localized endodermal expression of hhex and prox1 at 22 hours post fertilization...
- Klein C, Mikutta J, Krueger J, Scholz K, Brinkmann J, Liu D, et al. Neuron navigator 3a regulates liver organogenesis during zebrafish embryogenesis. Development. 2011;138:1935-45 pubmed publisher..We conclude that nav3a is required for directing endodermal organogenesis involving coordination of endodermal cell behavior. ..
- Wallace K, Yusuff S, Sonntag J, Chin A, Pack M. Zebrafish hhex regulates liver development and digestive organ chirality. Genesis. 2001;30:141-3 pubmed
- Chung W, Shin C, Stainier D. Bmp2 signaling regulates the hepatic versus pancreatic fate decision. Dev Cell. 2008;15:738-48 pubmed publisher..These data provide in vivo evidence for the existence of bipotential hepatopancreatic progenitors and indicate that their fate is regulated by the medio-lateral patterning of the endodermal sheet, a process controlled by Bmp2b. ..
- Ho C, Houart C, Wilson S, Stainier D. A role for the extraembryonic yolk syncytial layer in patterning the zebrafish embryo suggested by properties of the hex gene. Curr Biol. 1999;9:1131-4 pubmed..To analyze whether similar mechanisms operate in other vertebrates, we cloned the zebrafish homologue of Hex, a homeobox gene that is expressed asymmetrically in the mouse visceral endoderm ...
- Elsalini O, von Gartzen J, Cramer M, Rohr K. Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation downstream of Nodal-dependent transcription factors. Dev Biol. 2003;263:67-80 pubmedDuring zebrafish development, the thyroid primordium initiates expression of molecular markers such as hhex and nk2.1a in the endoderm prior to pharynx formation...
- Burke Z, Thowfeequ S, Tosh D. Liver specification: a new role for Wnts in liver development. Curr Biol. 2006;16:R688-90 pubmed..Secreted Wnt proteins control a diverse array of developmental decisions. A recent analysis of the zebrafish mutant prometheus points to a previously unknown role for Wnts during liver specification. ..
- Lancman J, Zvenigorodsky N, Gates K, Zhang D, Solomon K, Humphrey R, et al. Specification of hepatopancreas progenitors in zebrafish by hnf1ba and wnt2bb. Development. 2013;140:2669-79 pubmed publisher..Collectively, our findings provide a new model for HNF1B function, yield insight into pancreas and ?-cell development, and suggest a new mechanism for hepatopancreatic specification...
- Yu L, Lam J, Guo Y, Wu R, Lam P, Zhou B. Parental transfer of polybrominated diphenyl ethers (PBDEs) and thyroid endocrine disruption in zebrafish. Environ Sci Technol. 2011;45:10652-9 pubmed publisher..For the first time, we demonstrated that parental exposure to low concentrations of PBDEs could affect THs in the offspring and the transgenerational PBDE-induced toxicity in subsequent nonexposed generations. ..
- Qi F, Song J, Yang H, Gao W, Liu N, Zhang B, et al. Mmp23b promotes liver development and hepatocyte proliferation through the tumor necrosis factor pathway in zebrafish. Hepatology. 2010;52:2158-66 pubmed publisher..Because mmp23b/MMP23B is highly conserved, our findings in zebrafish warrant further investigation of its role in regulating liver development in mammals. ..
- Rohde L, Oates A, Ho R. A crucial interaction between embryonic red blood cell progenitors and paraxial mesoderm revealed in spadetail embryos. Dev Cell. 2004;7:251-62 pubmed..Importantly, our data identify a hematopoietic microenvironment that allows embryonic RBC production in the zebrafish. ..
- Naye F, Voz M, Detry N, Hammerschmidt M, Peers B, Manfroid I. Essential roles of zebrafish bmp2a, fgf10, and fgf24 in the specification of the ventral pancreas. Mol Biol Cell. 2012;23:945-54 pubmed publisher..These mutants display ventral pancreas agenesis and ectopic masses of hepatocytes. Overall, these data highlight the dynamic role of BMP and FGF in the patterning of the hepatopancreatic region. ..
- Latimer A, Jessen J. Hgf/c-met expression and functional analysis during zebrafish embryogenesis. Dev Dyn. 2008;237:3904-15 pubmed publisher..Similar to mouse, knockdown of zebrafish Met reduces liver size. Our results suggest a role for Met during endoderm specification and indicate that mechanisms of liver development are conserved between mammals and bony fish. ..
- Shi X, Du Y, Lam P, Wu R, Zhou B. Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS. Toxicol Appl Pharmacol. 2008;230:23-32 pubmed publisher..In addition, we investigated the effects of PFOS on marker genes related to early thyroid development (hhex and pax8) and genes regulating the balance of androgens and estrogens (cyp19a and cyp19b)...
- Zucchi S, Blüthgen N, Ieronimo A, Fent K. The UV-absorber benzophenone-4 alters transcripts of genes involved in hormonal pathways in zebrafish (Danio rerio) eleuthero-embryos and adult males. Toxicol Appl Pharmacol. 2011;250:137-46 pubmed publisher..In eleuthero-embryos transcripts of vtg1, vtg3, esr1, esr2b, hsd17ß3, cyp19b cyp19a, hhex and pax8 were induced at 3000 ?g/L BP-4, which points to a low estrogenic activity and interference with early ..
- Won M, Ro H, Dawid I. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas. Proc Natl Acad Sci U S A. 2015;112:12426-31 pubmed publisher..Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use. ..
- Du G, Hu J, Huang H, Qin Y, Han X, Wu D, et al. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo. Environ Toxicol Chem. 2013;32:353-60 pubmed publisher..In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, ..
- Takeuchi M, Fuse Y, Watanabe M, Andrea C, Takeuchi M, Nakajima H, et al. LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2. Proc Natl Acad Sci U S A. 2015;112:13922-7 pubmed publisher..Our results suggest that the LSD1-dependent shutdown of Etv2 gene expression may be a significant event required for hemangioblasts to initiate hematopoietic differentiation. ..
- Lu H, Ma J, Yang Y, Shi W, Luo L. EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development. Dev Cell. 2013;24:543-53 pubmed publisher..Our results identify EpCAM as the key molecule and its functional mechanism to confer endodermal cells the competence to respond to the liver-inductive Wnt2bb signal. ..
- Chang C, Hu M, Zhu Z, Lo L, Chen J, Peng J. liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish. PLoS ONE. 2011;6:e22910 pubmed publisher..Finally, we proved that Leg1 is a secretory protein. This intrigued us to propose that Leg1 might act as a novel secreted regulator that is essential for liver and other digestive organ development in zebrafish. ..
- Zhai G, Song J, Shu T, Yan J, Jin X, He J, et al. LRH-1 senses signaling from phosphatidylcholine to regulate the expansion growth of digestive organs via synergy with Wnt/Î²-catenin signaling in zebrafish. J Genet Genomics. 2017;44:307-317 pubmed publisher..These data provide evidence for the crosstalk between the PC/LRH-1 and Wnt/Î²-catenin signaling pathways during the expansion growth of endoderm organs. ..
- Wang Y, Luo Y, Hong Y, Peng J, Lo L. Ribosome biogenesis factor Bms1-like is essential for liver development in zebrafish. J Genet Genomics. 2012;39:451-62 pubmed publisher..Therefore, our findings demonstrate that Bms1l is necessary for zebrafish liver development...
- Niu X, Gao C, Jan Lo L, Luo Y, Meng C, Hong J, et al. Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish. Dev Biol. 2012;367:197-207 pubmed publisher..Our data provide the first direct genetic evidence that COPII function is essential for the organogenesis of the digestive system...
- Weiser D, Pyati U, Kimelman D. Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation. Genes Dev. 2007;21:1559-71 pubmed
- Hu M, Bai Y, Zhang C, Liu F, Cui Z, Chen J, et al. Liver-Enriched Gene 1, a Glycosylated Secretory Protein, Binds to FGFR and Mediates an Anti-stress Pathway to Protect Liver Development in Zebrafish. PLoS Genet. 2016;12:e1005881 pubmed publisher..Therefore, Leg1 plays a unique role in protecting liver development under different stress conditions by serving as a secreted signaling molecule/modulator. ..
- Kim S, Sohn J, Ha S, Kang H, Yim U, Shim W, et al. Thyroid Hormone Disruption by Water-Accommodated Fractions of Crude Oil and Sediments Affected by the Hebei Spirit Oil Spill in Zebrafish and GH3 Cells. Environ Sci Technol. 2016;50:5972-80 pubmed publisher..Sediment samples also showed thyroid disrupting potentials in the GH3 cell, even several years after the oil spill. Long-term ecosystem consequences of thyroid hormone disruption due to oil spill deserve further investigation. ..
- Nissim S, Sherwood R, Wucherpfennig J, Saunders D, Harris J, Esain V, et al. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell. 2014;28:423-37 pubmed publisher..This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell-fate decisions and outgrowth of the embryonic endodermal anlagen. ..
- Liu L, Fox C, North T, Goessling W. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development. Dis Model Mech. 2013;6:1271-8 pubmed publisher..Our analysis can be extended to GWAS for additional disease-associated phenotypes...
- Nissim S, Weeks O, Talbot J, Hedgepeth J, Wucherpfennig J, Schatzman Bone S, et al. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Dev Biol. 2016;418:108-123 pubmed publisher..These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. ..
- Faro A, Boj S, Ambrósio R, van den Broek O, Korving J, Clevers H. T-cell factor 4 (tcf7l2) is the main effector of Wnt signaling during zebrafish intestine organogenesis. Zebrafish. 2009;6:59-68 pubmed publisher..This study reveals that Tcf4 (tcf7l2) is the major effector of Wnt signaling in the intestine during zebrafish organogenesis. ..
- Cox A, Saunders D, Kelsey P, Conway A, Tesmenitsky Y, Marchini J, et al. S-nitrosothiol signaling regulates liver development and improves outcome following toxic liver injury. Cell Rep. 2014;6:56-69 pubmed publisher..These studies demonstrate that GSNOR inhibitors will be beneficial therapeutic candidates for treating liver injury...
- Ko S, Choi T, Russell J, So J, Monga S, Shin D. Bromodomain and extraterminal (BET) proteins regulate biliary-driven liver regeneration. J Hepatol. 2016;64:316-325 pubmed publisher..BET proteins regulate BEC-driven liver regeneration at multiple steps: BEC dedifferentiation, HB-LC proliferation, the proliferation of newly generated hepatocytes, and hepatocyte maturation. ..
- Khaliq M, Choi T, So J, Shin D. Id2a is required for hepatic outgrowth during liver development in zebrafish. Mech Dev. 2015;138 Pt 3:399-414 pubmed publisher..Altogether, these data support the role of Id2a as an important regulator of hepatic outgrowth via modulation of hepatoblast proliferation and survival during liver development in zebrafish. ..
- Xu J, Cui J, del Campo A, Shin C. Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for Î²-Cell Regeneration. PLoS Genet. 2016;12:e1005831 pubmed publisher..Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in Î²-cell regeneration. ..
- He J, Lu H, Zou Q, Luo L. Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. Gastroenterology. 2014;146:789-800.e8 pubmed publisher..Using our zebrafish liver regeneration model, we found that biliary cells can transdifferentiate into hepatocytes and are the major contributors to hepatocyte regeneration after extreme hepatocyte loss...
- Opitz R, Maquet E, Zoenen M, Dadhich R, Costagliola S. TSH receptor function is required for normal thyroid differentiation in zebrafish. Mol Endocrinol. 2011;25:1579-99 pubmed publisher..A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. ..
- Hong S, Dawid I. Alpha2 macroglobulin-like is essential for liver development in zebrafish. PLoS ONE. 2008;3:e3736 pubmed publisher..This report on A2ML function in zebrafish development provides the first evidence for a specific role of an A2M family gene in liver formation during early embryogenesis in a vertebrate. ..
- Wei S, Ning G, Li L, Yan Y, Yang S, Cao Y, et al. A GEF activity-independent function for nuclear Net1 in Nodal signal transduction and mesendoderm formation. J Cell Sci. 2017;130:3072-3082 pubmed publisher..These findings describe a novel genetic mechanism by which nuclear Net1 facilitates Smad2 transcriptional activity to guide mesendoderm development. ..
- Wang Q, Liang K, Liu J, Yang L, Guo Y, Liu C, et al. Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic-pituitary-thyroid axis. Aquat Toxicol. 2013;126:207-13 pubmed publisher..transcription of genes involved in thyroid hormone synthesis (tsh?, slc5a5 and tg) and thyroid development (hhex, nkx2.1 and pax8) as a compensatory mechanism for decreased T4 concentrations...
- Kim S, Ji K, Lee S, Lee J, Kim J, Kim S, et al. Perfluorooctane sulfonic acid exposure increases cadmium toxicity in early life stage of zebrafish, Danio rerio. Environ Toxicol Chem. 2011;30:870-7 pubmed publisher..thyroid hormone receptor-alpha [THR?], thyroid hormone receptor-beta [THR?], hematopoietically expressed homeobox [hhex], and paired box gene 8 [pax8]) and decrease of throxine (T4) levels were observed in the PFOS preexposure group, ..
- Liu L, Alexa K, Cortes M, Schatzman Bone S, Kim A, Mukhopadhyay B, et al. Cannabinoid receptor signaling regulates liver development and metabolism. Development. 2016;143:609-22 pubmed publisher..Our work describes a novel developmental role for EC signaling, whereby Cnr-mediated regulation of Srebfs and methionine metabolism impacts liver development and function. ..
- Wendl T, Adzic D, Schoenebeck J, Scholpp S, Brand M, Yelon D, et al. Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals. Development. 2007;134:2871-9 pubmed..FGF-soaked beads can restore thyroid development in han mutants, showing that FGFs act downstream of or in parallel to han. These data suggest that loss of FGF-expressing tissue in han mutants is responsible for the thyroid defects. ..
- Anderson K, Singer R, Balderes D, Hernandez Lagunas L, Johnson C, Artinger K, et al. The L6 domain tetraspanin Tm4sf4 regulates endocrine pancreas differentiation and directed cell migration. Development. 2011;138:3213-24 pubmed publisher..Identification of a role for Tm4sf4 during endocrine differentiation provides insight into islet progenitor cell behaviors and potential targetable regenerative mechanisms. ..
- Rainieri S, Conlledo N, Langerholc T, Madorran E, Sala M, Barranco A. Toxic effects of perfluorinated compounds at human cellular level and on a model vertebrate. Food Chem Toxicol. 2017;104:14-25 pubmed publisher..This study highlights the importance of studying PFCs in realistic conditions on various biological models. ..
- Cayuso J, Dzementsei A, Fischer J, Karemore G, Caviglia S, Bartholdson J, et al. EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality. Dev Cell. 2016;39:316-328 pubmed publisher..We propose that bidirectional short- and long-distance cell interactions between epithelial and mesenchyme-like tissues coordinate liver bud formation and laterality via cell repulsion. ..
- Porreca I, De Felice E, Fagman H, Di Lauro R, Sordino P. Zebrafish bcl2l is a survival factor in thyroid development. Dev Biol. 2012;366:142-52 pubmed publisher..1a and hhex. Also, the bcl2l gene appears to control a caspase-3-dependent apoptotic mechanism during thyroid development...
- Hsia N, Zon L. Transcriptional regulation of hematopoietic stem cell development in zebrafish. Exp Hematol. 2005;33:1007-14 pubmed..Future studies using new technologies in the zebrafish model will enhance our understanding of the molecular networks regulating HSC pluripotency and differentiation. ..
- Li Y, Chiang K, Li Y, Wu S, Liu W, Lin C, et al. MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. PLoS ONE. 2017;12:e0177887 pubmed publisher..In conclusion, our findings suggest an important role of miR-145 in regulating GrnA-dependent hepatic outgrowth in zebrafish embryonic development. ..
- Alexa K, Choe S, Hirsch N, Etheridge L, Laver E, SAGERSTROM C. Maternal and zygotic aldh1a2 activity is required for pancreas development in zebrafish. PLoS ONE. 2009;4:e8261 pubmed publisher..expression is less affected in the mutant, with varying degrees of residual expression observed for pdx1, carbA, hhex, prox1, sid4, transferrin and ifabp. In addition, mutant embryos display a swollen pericardium and lack fin buds...
- Lam E, Chau J, Kalev Zylinska M, Fountaine T, Mead R, Hall C, et al. Zebrafish runx1 promoter-EGFP transgenics mark discrete sites of definitive blood progenitors. Blood. 2009;113:1241-9 pubmed publisher..The ability to visualize and isolate fluorescently labeled HSCs should contribute to further elucidating the complex regulation of HSC development. ..
- Kumari P, Gilligan P, Lim S, Tran L, Winkler S, Philp R, et al. An essential role for maternal control of Nodal signaling. elife. 2013;2:e00683 pubmed publisher..Thus, Ybx1 prevents ectopic Nodal activity, revealing a new paradigm in the regulation of Nodal signaling, which is likely to be conserved. DOI:http://dx.doi.org/10.7554/eLife.00683.001. ..
- Gao M, Yan H, Yin R, Wang Q, Zhan Y, Yu M, et al. Hepassocin is required for hepatic outgrowth during zebrafish hepatogenesis. Biochem Biophys Res Commun. 2015;463:466-71 pubmed publisher..that the HPS knockdown has no effect on the expression of the early endoderm marker gata6 and early hepatic marker hhex. In addition, results showed that the smaller-liver phenotype in HPS morphants was caused by suppression of cell ..
- Yuan H, Wen B, Liu X, Gao C, Yang R, Wang L, et al. CCAAT/enhancer-binding protein Î± is required for hepatic outgrowth via the p53 pathway in zebrafish. Sci Rep. 2015;5:15838 pubmed publisher..Thus, our findings for the first time demonstrate a stage-specific role for C/ebpÎ± during liver organogenesis. ..
- Wu S, Shin J, Sepich D, Solnica Krezel L. Chemokine GPCR signaling inhibits ?-catenin during zebrafish axis formation. PLoS Biol. 2012;10:e1001403 pubmed publisher..Our study delineates a novel negative, Gsk3?-independent control mechanism of ?-catenin and implicates Ccr7 as a long-hypothesized GPCR regulating vertebrate axis formation. ..
- 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. ..
- Qin W, Chen Z, Zhang Y, Yan R, Yan G, Li S, et al. Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish. PLoS ONE. 2014;9:e100796 pubmed publisher..This suggests that targeting Pp1? into the nucleolus by Nom1 is important for pancreatic proliferation. Altogether, our studies revealed a new mechanism involving Nom1 in controlling vertebrate exocrine pancreas formation. ..
- Du G, Huang H, Hu J, Qin Y, Wu D, Song L, et al. Endocrine-related effects of perfluorooctanoic acid (PFOA) in zebrafish, H295R steroidogenesis and receptor reporter gene assays. Chemosphere. 2013;91:1099-106 pubmed publisher..Exposure of zebrafish embryo to PFOA resulted in higher expression of esr1, hhex and pax. PFOA is able to interfere with hormone receptor ER and TR...
- Bischof J, Driever W. Regulation of hhex expression in the yolk syncytial layer, the potential Nieuwkoop center homolog in zebrafish. Dev Biol. 2004;276:552-62 pubmed..the anterior endomesoderm in frogs (Xhex), the anterior visceral endoderm in mice, and the dorsal YSL in zebrafish (hhex). Here, we investigate the control of hhex expression in the YSL...
- Stuckenholz C, Lu L, Thakur P, Choi T, Shin D, Bahary N. Sfrp5 modulates both Wnt and BMP signaling and regulates gastrointestinal organogenesis [corrected] in the zebrafish, Danio rerio. PLoS ONE. 2013;8:e62470 pubmed publisher..We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities...