Genomes and Genes
Gene Symbol: nkx2.2a
Description: NK2 homeobox 2a
Alias: id:ibd5090, nk2.2, nkx2-2, nkx2.2, wu:fc83b01, zgc:136536, homeobox protein Nkx-2.2a, NK2 transcription factor related 2a, homeobox protein NK-2 homolog B-A
- Teraoka H, Russell C, Regan J, Chandrasekhar A, Concha M, Yokoyama R, et al. Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos. J Neurobiol. 2004;60:275-88 pubmed..Our results show that the pathways involved in induction of hindbrain serotonergic neurons are likely to be conserved in all vertebrates and help establish the zebrafish as a model system to study this important neuronal class. ..
- Nakano Y, Kim H, Kawakami A, Roy S, Schier A, Ingham P. Inactivation of dispatched 1 by the chameleon mutation disrupts Hedgehog signalling in the zebrafish embryo. Dev Biol. 2004;269:381-92 pubmed
- Ng A, de Jong Curtain T, Mawdsley D, White S, Shin J, Appel B, et al. Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis. Dev Biol. 2005;286:114-35 pubmed..At 126 hpf, the posterior intestine remains an unfolded monolayer of simple columnar epithelium. ..
- Koudijs M, den Broeder M, Groot E, van Eeden F. Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway. BMC Dev Biol. 2008;8:15 pubmed publisher..Additionally, these mutants will provide a useful system to further investigate the consequences of constitutively activated Hh signaling during vertebrate development. ..
- Ben J, Elworthy S, Ng A, van Eeden F, Ingham P. Targeted mutation of the talpid3 gene in zebrafish reveals its conserved requirement for ciliogenesis and Hedgehog signalling across the vertebrates. Development. 2011;138:4969-78 pubmed publisher..Our findings underline the importance of the primary cilium for Hh signaling in zebrafish and reveal the conservation of Ta3 function during vertebrate evolution...
- Ribes V, Balaskas N, Sasai N, Cruz C, Dessaud E, Cayuso J, et al. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube. Genes Dev. 2010;24:1186-200 pubmed publisher..In addition, we provide evidence supporting a common scheme for FP specification by Shh signaling that reconciles mechanisms of FP development in teleosts and amniotes. ..
- Guner B, Karlstrom R. Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube. Gene Expr Patterns. 2007;7:596-605 pubmed
- Yang L, Rastegar S, Strahle U. Regulatory interactions specifying Kolmer-Agduhr interneurons. Development. 2010;137:2713-22 pubmed publisher..Instead, olig2 and gata3 are required for the differentiation of gad67-expressing KA' cells. This suggests that the layout of regulatory networks is crucially dependent on the lineage that differs between KA' and KA' cells. ..
- Schafer M, Kinzel D, Winkler C. Discontinuous organization and specification of the lateral floor plate in zebrafish. Dev Biol. 2007;301:117-29 pubmed..We conclude that different levels of HH and Nkx2.2 activities are responsible for the alternating appearance of LFP and p3 neuronal progenitor cells in the zebrafish ventral neural tube. ..
- Woods I, Talbot W. The you gene encodes an EGF-CUB protein essential for Hedgehog signaling in zebrafish. PLoS Biol. 2005;3:e66 pubmed..Our positional cloning and functional studies demonstrate that You is a novel extracellular component of the Hedgehog pathway in vertebrates. ..
- Tyurina O, Guner B, Popova E, Feng J, Schier A, Kohtz J, et al. Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling. Dev Biol. 2005;277:537-56 pubmed..These results reveal a conserved role for Gli3 in vertebrate development and uncover novel regional functions and regulatory interactions among gli genes. ..
- Norton W, Mangoli M, Lele Z, Pogoda H, Diamond B, Mercurio S, et al. Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones. Development. 2005;132:645-58 pubmed
- Cui Y, Lv S, Liu J, Nie S, Chen J, Dong Q, et al. Chronic perfluorooctanesulfonic acid exposure disrupts lipid metabolism in zebrafish. Hum Exp Toxicol. 2017;36:207-217 pubmed publisher..These findings provided evidence that PFOS chronic exposure adversely impacts lipid metabolism in both F0 and F1 and demonstrated the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening. ..
- Gribble S, Kim H, Bonner J, Wang X, Dorsky R. Tcf3 inhibits spinal cord neurogenesis by regulating sox4a expression. Development. 2009;136:781-9 pubmed publisher..Both of these functions are mediated by Tcf3 independently of canonical Wnt signaling. Together, our data indicate a novel mechanism for the regulation of neurogenesis by Tcf3-mediated repression. ..
- Cardozo M, Sánchez Arrones L, Sandonìs A, Sánchez Camacho C, Gestri G, Wilson S, et al. Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle. Nat Commun. 2014;5:4272 pubmed publisher..This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. ..
- Feng J, White B, Tyurina O, Guner B, Larson T, Lee H, et al. Synergistic and antagonistic roles of the Sonic hedgehog N- and C-terminal lipids. Development. 2004;131:4357-70 pubmed
- Cunliffe V, Casaccia Bonnefil P. Histone deacetylase 1 is essential for oligodendrocyte specification in the zebrafish CNS. Mech Dev. 2006;123:24-30 pubmed
- Vanderlaan G, Tyurina O, Karlstrom R, Chandrasekhar A. Gli function is essential for motor neuron induction in zebrafish. Dev Biol. 2005;282:550-70 pubmed..These observations demonstrate that Gli activator function (encoded by gli1, gli2, and gli3) is essential for motor neuron induction and Hh-regulated gene expression in zebrafish. ..
- Liu S, Li Z, Gui J. Fish-specific duplicated dmrt2b contributes to a divergent function through Hedgehog pathway and maintains left-right asymmetry establishment function. PLoS ONE. 2009;4:e7261 pubmed publisher..Together, these data indicate that fish-specific duplicated dmrt2b contributes to a divergent function in somitogenesis through Hedgehog pathway and maintains the common function for left-right asymmetry establishment. ..
- Tiso N, Filippi A, Benato F, Negrisolo E, Modena N, Vaccari E, et al. Differential expression and regulation of olig genes in zebrafish. J Comp Neurol. 2009;515:378-96 pubmed publisher..Our findings suggest a role for olig genes in CNS patterning as well as in multiple cell fate decisions during neural differentiation. ..
- Mahler J, Filippi A, Driever W. DeltaA/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish. J Neurosci. 2010;30:16621-35 pubmed publisher..Rather, DeltaA/D limits the size of the sim1a- and otpa-expressing precursor pool from which dopaminergic neurons differentiate. ..
- Flasse L, Stern D, Pirson J, Manfroid I, Peers B, Voz M. The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine. Dev Biol. 2013;376:187-97 pubmed publisher..This highlights the diversity in the ARP/ASCL family members acting as cell fate determinants downstream from Notch signaling. ..
- Wang F, Chen X, Shi W, Yao L, Gao M, Yang Y, et al. Zdhhc15b Regulates Differentiation of Diencephalic Dopaminergic Neurons in zebrafish. J Cell Biochem. 2015;116:2980-91 pubmed publisher..Our results reveal that zdhhc15b controls DA neuronal fate decisions by regulating differentiation but not progenitor cell proliferation or DA neuronal survival. ..
- Ellertsdottir E, Ganz J, Durr K, Loges N, Biemar F, Seifert F, et al. A mutation in the zebrafish Na,K-ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left-right asymmetry downstream or in parallel to nodal flow. Dev Dyn. 2006;235:1794-808 pubmed..Therefore, the Na,K-ATPase is required downstream or in parallel to monocilia function during initiation of left-right asymmetry in zebrafish. ..
- Gongal P, March L, Holly V, Pillay L, Berry Wynne K, Kagechika H, et al. Hmx4 regulates Sonic hedgehog signaling through control of retinoic acid synthesis during forebrain patterning. Dev Biol. 2011;355:55-64 pubmed publisher..We propose that Hmx4 is a critical regulator of retinoic acid synthesis in a developing embryo, and that this regulation is essential for controlling Shh signaling and forebrain development. ..
- Chen Y, Lu Y, Ko T, Tsai M, Lin C, Lin C, et al. Zebrafish cdx1b regulates differentiation of various intestinal cell lineages. Dev Dyn. 2009;238:1021-32 pubmed publisher..Overall, our results suggest that zebrafish cdx1b plays important roles in regulating intestinal cell proliferation and the differentiation of various intestinal cell lineages. ..
- Arnold C, Lamont R, Walker J, Spice P, Chan C, Ho C, et al. Comparative analysis of genes regulated by Dzip1/iguana and hedgehog in zebrafish. Dev Dyn. 2015;244:211-23 pubmed publisher..Through comparing gene expression changes in a genetic model of vascular instability with a chemical inhibition of Hh signaling, we identified a set of 40 differentially expressed genes with potential roles in vascular stabilization. ..
- Rohr K, Barth K, Varga Z, Wilson S. The nodal pathway acts upstream of hedgehog signaling to specify ventral telencephalic identity. Neuron. 2001;29:341-51 pubmed..Thus, the Nodal pathway regulates ventral forebrain patterning through both Hedgehog signaling-dependent and -independent mechanisms. ..
- Sidik H, Talbot W. A zinc finger protein that regulates oligodendrocyte specification, migration and myelination in zebrafish. Development. 2015;142:4119-28 pubmed publisher..Our results defined the function of a new zinc finger protein with specific function in oligodendrocyte specification, migration and myelination in the developing CNS. ..
- Anderson K, Torres C, Solomon K, Becker T, Newgard C, Wright C, et al. Cooperative transcriptional regulation of the essential pancreatic islet gene NeuroD1 (beta2) by Nkx2.2 and neurogenin 3. J Biol Chem. 2009;284:31236-48 pubmed publisher..Collectively, these findings further define the conserved regulatory networks involved in islet beta cell formation and function. ..
- Zhai G, Gu Q, He J, Lou Q, Chen X, Jin X, et al. Sept6 is required for ciliogenesis in Kupffer's vesicle, the pronephros, and the neural tube during early embryonic development. Mol Cell Biol. 2014;34:1310-21 pubmed publisher..Our study reveals a novel role of sept6 in ciliogenesis during early embryonic development in zebrafish. ..
- Al Oustah A, Danesin C, Khouri Farah N, Farreny M, Escalas N, Cochard P, et al. Dynamics of sonic hedgehog signaling in the ventral spinal cord are controlled by intrinsic changes in source cells requiring sulfatase 1. Development. 2014;141:1392-403 pubmed publisher..Our work, by pointing out the key role of Sulf1 in regulating Shh-dependent neural cell diversity, highlights a novel level of regulation, which involves temporal evolution of Shh source properties. ..
- Wang X, Zhao Z, Müller J, Iyu A, Khng A, Guccione E, et al. Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish. Biol Open. 2013;2:1203-13 pubmed publisher..Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a. ..
- Ochi H, Pearson B, Chuang P, Hammerschmidt M, Westerfield M. Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened. Dev Biol. 2006;297:127-40 pubmed..These data support a model in which Hhip regulates muscle development both by sequestering Hedgehog and by modulating localization of Smoothened. ..
- Kucenas S, Snell H, Appel B. nkx2.2a promotes specification and differentiation of a myelinating subset of oligodendrocyte lineage cells in zebrafish. Neuron Glia Biol. 2008;4:71-81 pubmed publisher..We conclude that Nkx2.2 promotes timely specification and differentiation of myelinating oligodendrocyte lineage cells from species representing different vertebrate taxa. ..
- Li Y, Yang H, Zdanowicz M, Sicklick J, Qi Y, Camp T, et al. Fetal alcohol exposure impairs Hedgehog cholesterol modification and signaling. Lab Invest. 2007;87:231-40 pubmed..This insight into FASD pathogenesis may suggest novel strategies for preventing these common congenital defects. ..
- Philipp M, Fralish G, Meloni A, Chen W, MacInnes A, BARAK L, et al. Smoothened signaling in vertebrates is facilitated by a G protein-coupled receptor kinase. Mol Biol Cell. 2008;19:5478-89 pubmed publisher..Together, these data suggest that a GRK functions as a vertebrate kinase for Smoothened, promoting Hedgehog signal transduction during early development. ..
- Esain V, Postlethwait J, Charnay P, Ghislain J. FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9. Development. 2010;137:33-42 pubmed publisher..Overall, for the first time in vivo, our results reveal a mechanism of FGF in the control of neural cell diversity. ..
- Gates K, Mentzer L, Karlstrom R, Sirotkin H. The transcriptional repressor REST/NRSF modulates hedgehog signaling. Dev Biol. 2010;340:293-305 pubmed publisher..The role of Rest as a regulator of Hh signaling has broad implications for many developmental contexts where REST and Hh signaling act. ..
- Zecchin E, Filippi A, Biemar F, Tiso N, Pauls S, Ellertsdottir E, et al. Distinct delta and jagged genes control sequential segregation of pancreatic cell types from precursor pools in zebrafish. Dev Biol. 2007;301:192-204 pubmed
- Pauls S, Zecchin E, Tiso N, Bortolussi M, Argenton F. Function and regulation of zebrafish nkx2.2a during development of pancreatic islet and ducts. Dev Biol. 2007;304:875-90 pubmed..2a in the development of the pancreatic ducts. ..
- Hauptmann G, Söll I, Gerster T. The early embryonic zebrafish forebrain is subdivided into molecularly distinct transverse and longitudinal domains. Brain Res Bull. 2002;57:371-5 pubmed..Furthermore, we identified a series of eight transverse diencephalic domains which may indicate a prosomeric organization of the rostral zebrafish brain. ..
- Schebesta M, Serluca F. olig1 Expression identifies developing oligodendrocytes in zebrafish and requires hedgehog and notch signaling. Dev Dyn. 2009;238:887-98 pubmed publisher..Lastly, knockdown of Olig1 in an Olig2-sensitized background did result in defects in CNS myelination, indicating a functional overlap between Olig1 and Olig2 proteins. ..
- Sonnack L, Klawonn T, Kriehuber R, Hollert H, Schäfers C, Fenske M. Concentration dependent transcriptome responses of zebrafish embryos after exposure to cadmium, cobalt and copper. Comp Biochem Physiol Part D Genomics Proteomics. 2017;24:29-40 pubmed publisher..Some of these genes may be indicative of the mechanisms of action of the individual metals in zebrafish embryos. Real-time quantitative RT-PCR (qRT-PCR) verified the microarray data for mmp9, mt2, cldnb and nkx2.2a. ..
- Jacob J, Ribes V, Moore S, Constable S, Sasai N, Gerety S, et al. Valproic acid silencing of ascl1b/Ascl1 results in the failure of serotonergic differentiation in a zebrafish model of fetal valproate syndrome. Dis Model Mech. 2014;7:107-17 pubmed publisher..Together, these data provide a molecular explanation for serotonergic defects in FVS and highlight an epigenetic mechanism for genome-environment interaction in disease. ..
- Shi W, Chen X, Wang F, Gao M, Yang Y, Du Z, et al. ZDHHC16 modulates FGF/ERK dependent proliferation of neural stem/progenitor cells in the zebrafish telencephalon. Dev Neurobiol. 2016;76:1014-28 pubmed publisher..2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1014-1028, 2016. ..
- Zannino D, Downes G, SAGERSTROM C. prdm12b specifies the p1 progenitor domain and reveals a role for V1 interneurons in swim movements. Dev Biol. 2014;390:247-60 pubmed publisher..We conclude that prdm12b is required for V1 interneuron specification and that these neurons control swimming movements in zebrafish. ..
- Chandrasekhar A, Schauerte H, Haffter P, Kuwada J. The zebrafish detour gene is essential for cranial but not spinal motor neuron induction. Development. 1999;126:2727-37 pubmed
- Philipp M, Berger I, Just S, Caron M. Overlapping and opposing functions of G protein-coupled receptor kinase 2 (GRK2) and GRK5 during heart development. J Biol Chem. 2014;289:26119-30 pubmed publisher..In summary, we found that GRK2 and GRK5 control cardiac function as well as morphogenesis during development although with different morphological outcomes. ..
- Yamamoto T, Tsukahara T, Ishiguro T, Hagiwara H, Taira M, Takeda H. The medaka dhc2 mutant reveals conserved and distinct mechanisms of Hedgehog signaling in teleosts. BMC Dev Biol. 2015;15:9 pubmed publisher..The finding of this fish-specific augmentation provides a novel insight into the evolution of Hh signaling. ..
- Shinya M, Furutani Seiki M, Kuroiwa A, Takeda H. Mosaic analysis with oep mutant reveals a repressive interaction between floor-plate and non-floor-plate mutant cells in the zebrafish neural tube. Dev Growth Differ. 1999;41:135-42 pubmed
- Kucenas S, Takada N, Park H, Woodruff E, Broadie K, Appel B. CNS-derived glia ensheath peripheral nerves and mediate motor root development. Nat Neurosci. 2008;11:143-51 pubmed publisher..These insights reveal a new class of CNS-born glia that critically contributes to motor nerve development. ..
- Evron T, Philipp M, Lu J, Meloni A, Burkhalter M, Chen W, et al. Growth Arrest Specific 8 (Gas8) and G protein-coupled receptor kinase 2 (GRK2) cooperate in the control of Smoothened signaling. J Biol Chem. 2011;286:27676-86 pubmed publisher..This is in contrast to cells stably expressing both GRK2 and Smo, in which cilia are significantly elongated. These results identify Gas8 as a positive regulator of Hh signaling that cooperates with GRK2 to control Smo signaling. ..
- Gribble S, Nikolaus O, Dorsky R. Regulation and function of Dbx genes in the zebrafish spinal cord. Dev Dyn. 2007;236:3472-83 pubmed..Our data confirm that the dbx1a/1b/2 domain in zebrafish spinal cord development behaves similarly to amniotes, while extending knowledge of Dbx1 function in spinal cord patterning. ..
- Leacock S, Basse A, Chandler G, Kirk A, Rakheja D, Amatruda J. A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis. Dis Model Mech. 2012;5:95-106 pubmed publisher..These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene. ..
- Guner B, Ozacar A, Thomas J, Karlstrom R. Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis. Endocrinology. 2008;149:4435-51 pubmed publisher..These data suggest that there are distinct origins and signaling requirements for the PD and PI. ..
- Rohr K, Concha M. Expression of nk2.1a during early development of the thyroid gland in zebrafish. Mech Dev. 2000;95:267-70 pubmed..We therefore suggest that nk2.1a labels the thyroid precursor cells from somitogenesis stages onwards. ..
- Levkowitz G, Zeller J, Sirotkin H, French D, Schilbach S, Hashimoto H, et al. Zinc finger protein too few controls the development of monoaminergic neurons. Nat Neurosci. 2003;6:28-33 pubmed..Our results indicate that tof/fezl is a key component in regulating the development of monoaminergic neurons in the vertebrate brain. ..
- Zhao Z, Lee R, Pusapati G, Iyu A, Rohatgi R, Ingham P. An essential role for Grk2 in Hedgehog signalling downstream of Smoothened. EMBO Rep. 2016;17:739-52 pubmed publisher..Since Grk2 rescuing activity requires the integrity of domains essential for its interaction with GPCRs, we speculate that Grk2 may regulate Hh pathway activity by downregulation of a GPCR. ..
- Hesselson D, Anderson R, Beinat M, Stainier D. Distinct populations of quiescent and proliferative pancreatic beta-cells identified by HOTcre mediated labeling. Proc Natl Acad Sci U S A. 2009;106:14896-901 pubmed publisher..g., diabetes mellitus). Our data reveal the existence of distinct populations of beta-cells in vivo and should help develop better strategies to regulate beta-cell differentiation and proliferation. ..
- Saita S, Shirane M, Ishitani T, Shimizu N, Nakayama K. Role of the ANKMY2-FKBP38 axis in regulation of the Sonic hedgehog (Shh) signaling pathway. J Biol Chem. 2014;289:25639-54 pubmed publisher..Our findings thus indicate that the FKBP38-ANKMY2 axis plays a key role in regulation of Shh signaling in vivo. ..
- Parsons M, Pisharath H, Yusuff S, Moore J, Siekmann A, Lawson N, et al. Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech Dev. 2009;126:898-912 pubmed publisher..We also show that Notch-responsive cells persist in the adult pancreas and possess the classical characteristics of centroacinar cells, a cell type believed to be a multipotent progenitor cell in adult mammalian pancreas. ..
- Ackerman S, Garcia C, Piao X, Gutmann D, Monk K. The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with GÎ±12/13 and RhoA. Nat Commun. 2015;6:6122 pubmed publisher..Finally, we show that these functions are mediated by GÎ±12/13 proteins and Rho activation. Together, our data establish Gpr56 as a regulator of oligodendrocyte development. ..
- Mavropoulos A, Devos N, Biemar F, Zecchin E, Argenton F, Edlund H, et al. sox4b is a key player of pancreatic alpha cell differentiation in zebrafish. Dev Biol. 2005;285:211-23 pubmed..Taken together, these data demonstrate that, in zebrafish, sox4b is expressed transiently during endocrine cell differentiation and plays a crucial role in the generation of alpha endocrine cells. ..
- Corallo D, Schiavinato A, Trapani V, Moro E, Argenton F, Bonaldo P. Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals. Development. 2013;140:4594-601 pubmed publisher..Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked. ..
- Levic D, Minkel J, Wang W, Rybski W, Melville D, Knapik E. Animal model of Sar1b deficiency presents lipid absorption deficits similar to Anderson disease. J Mol Med (Berl). 2015;93:165-76 pubmed publisher..Key messages: Sar1b depletion phenotype in zebrafish resembles Anderson disease deficits. Sar1b deficiency results in multi-organ developmental deficits. Sar1b is required for dietary cholesterol uptake into enterocytes. ..
- Eaton J, Glasgow E. Zebrafish orthopedia (otp) is required for isotocin cell development. Dev Genes Evol. 2007;217:149-58 pubmed..Overall, these studies support the hypothesis that the role of otp in zebrafish neuroendocrine cell development is evolutionarily conserved with that of mammals. ..
- Kunwar P, Zimmerman S, Bennett J, Chen Y, Whitman M, Schier A. Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction. Development. 2003;130:5589-99 pubmed