Genomes and Genes
Gene Symbol: Nkx3-2
Description: NK3 homeobox 2
Alias: Bapx1, NKX3.2, Nkx-3.2, homeobox protein Nkx-3.2, bagpipe homeobox gene 1 homolog, bagpipe homeobox protein homolog 1, homeobox protein NK-3 homolog B, homeodomain protein Nkx-3.2
- Lettice L, Hecksher Sørensen J, Hill R. The role of Bapx1 (Nkx3.2) in the development and evolution of the axial skeleton. J Anat. 2001;199:181-7 pubmed..The Bapxl gene found in fish, amphibians, birds and mammals appears to have derived vertebrate specific functions sometime after the split between the jawless fish and gnathostomes...
- Kim D, Kempf H, Chen R, Lassar A. Characterization of Nkx3.2 DNA binding specificity and its requirement for somitic chondrogenesis. J Biol Chem. 2003;278:27532-9 pubmed..2, Nkx3.2-N200Q is unable to activate the chondrocyte differentiation program in somitic mesoderm, indicating that DNA binding by Nkx3.2 is critical for this factor to induce somitic chondrogenesis. ..
- Lengner C, Hassan M, Serra R, Lepper C, Van Wijnen A, Stein J, et al. Nkx3.2-mediated repression of Runx2 promotes chondrogenic differentiation. J Biol Chem. 2005;280:15872-9 pubmed..We postulate that Runx2 is a critical link in BMP-2-mediated initiation of mesenchymal chondrogenesis that results in activation of Sox9 at least in part through the Nkx3.2-dependent repression of Runx2. ..
- Tribioli C, Lufkin T. The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. Development. 1999;126:5699-711 pubmedOur previous studies in both mouse and human identified the Bapx1 homeobox gene, a member of the NK gene family, as one of the earliest markers for prechondrogenic cells that will subsequently undergo mesenchymal condensation, cartilage ..
- Akazawa H, Komuro I, Sugitani Y, Yazaki Y, Nagai R, Noda T. Targeted disruption of the homeobox transcription factor Bapx1 results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation. Genes Cells. 2000;5:499-513 pubmedNK homeobox genes have been shown to play important roles in cell-type specification and organogenesis. Murine Bapx1, a member of NK homeobox gene family, is expressed in all the cartilageous tissues that undergo endochondral bone ..
- Schneider A, Mijalski T, Schlange T, Dai W, Overbeek P, Arnold H, et al. The homeobox gene NKX3.2 is a target of left-right signalling and is expressed on opposite sides in chick and mouse embryos. Curr Biol. 1999;9:911-4 pubmed..2 was expressed predominantly on the left side. Thus, NKX3.2 transcripts accumulate on opposite sides of mouse and chick embryos although, in both the mouse and chick, NKX3.2 expression is controlled by the L-R signalling pathways. ..
- Takamoto N, You L, Moses K, Chiang C, Zimmer W, Schwartz R, et al. COUP-TFII is essential for radial and anteroposterior patterning of the stomach. Development. 2005;132:2179-89 pubmed..Our results are consistent with a functional link between hedgehog proteins and COUP-TFII, factors that are vital for epithelial-mesenchymal interactions. ..
- Jeong D, Choi J, Kim D. Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy. J Cell Physiol. 2017;232:78-90 pubmed publisher..J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. ..
- Huang H, Cotton J, Wang Y, Rajurkar M, Zhu L, Lewis B, et al. Specific requirement of Gli transcription factors in Hedgehog-mediated intestinal development. J Biol Chem. 2013;288:17589-96 pubmed publisher..Taken together, our study reveals, for the first time, the distinct roles of Gli proteins in intestine development and suggests SLRPs as novel regulators of smooth muscle cell differentiation. ..
- Choi S, Jeong D, Kim J, Lee B, Joeng K, Long F, et al. Indian Hedgehog signalling triggers Nkx3.2 protein degradation during chondrocyte maturation. Biochem J. 2012;443:789-98 pubmed publisher..Thus these results suggest that Ihh/Wnt5a signalling may play a role in negative regulation of Nkx3.2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis. ..
- Sakhneny L, Rachi E, Epshtein A, Guez H, Wald Altman S, Lisnyansky M, et al. Pancreatic Pericytes Support ?-Cell Function in a Tcf7l2-Dependent Manner. Diabetes. 2018;67:437-447 pubmed publisher..Our findings thus propose a potential cellular mechanism through which abnormal TCF7L2 activity predisposes individuals to diabetes and implicates abnormalities in the islet microenvironment in this disease. ..
- Kokubu C, Wilm B, Kokubu T, Wahl M, Rodrigo I, Sakai N, et al. Undulated short-tail deletion mutation in the mouse ablates Pax1 and leads to ectopic activation of neighboring Nkx2-2 in domains that normally express Pax1. Genetics. 2003;165:299-307 pubmed..Furthermore, we show that expression of Bapx1, a downstream target of Pax1, is more strongly affected in Pax1(Un-s) mutants than in Pax1-null mutants, ..
- Sivakamasundari V, Chan H, Yap S, Xing X, Kraus P, Lufkin T. New Bapx1(Cre-EGFP) mouse lines for lineage tracing and conditional knockout studies. Genesis. 2012;50:375-83 pubmed publisher..the internal ribosome entry site (IRES) and the 2A peptide multicistronic expression strategies, we report two new Bapx1 mouse lines with functional Bapx1 whereby Cre and enhanced green fluorescence protein (EGFP) are expressed ..
- Caronia Brown G, Yoshida M, Gulden F, Assimacopoulos S, Grove E. The cortical hem regulates the size and patterning of neocortex. Development. 2014;141:2855-65 pubmed publisher..Our findings reveal a much broader role for the hem in cortical development than previously recognized, and emphasize that two major signaling centers interact antagonistically to pattern cerebral cortex. ..
- You L, Takamoto N, Yu C, Tanaka T, Kodama T, DeMayo F, et al. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci U S A. 2005;102:16351-6 pubmed..Our finding suggests that COUP-TFII is a likely contributor to the formation of CDH in individuals with 15q deletions, and it may also be a potential contributor to some other Bochdalek-type of CDH. ..
- Lu J, Chang P, Richardson J, Gan L, Weiler H, Olson E. The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis. Proc Natl Acad Sci U S A. 2000;97:9525-30 pubmed..The homeobox genes Hox11 and Bapx1, shown previously to be essential regulators of spleen organogenesis, and a lacZ reporter introduced into the ..
- Stafford D, Dichmann D, Chang J, Harland R. Deletion of the sclerotome-enriched lncRNA PEAT augments ribosomal protein expression. Proc Natl Acad Sci U S A. 2017;114:101-106 pubmed publisher..RNA-seq on PEAT mutant embryos showed that loss of PEAT modestly increases bone morphogenetic protein target gene expression and also elevates the expression of a large subset of ribosomal protein mRNAs. ..
- Im S, Kim D. Nkx3.2 induces oxygen concentration-independent and lysosome-dependent degradation of HIF-1? to modulate hypoxic responses in chondrocytes. Cell Signal. 2017;36:127-138 pubmed publisher..Therefore, these results suggest that Nkx3.2-mediated HIF regulation may allow cartilage-specific avascularity under hypoxic conditions during endochondral skeleton development. ..
- Santagati F, Minoux M, Ren S, Rijli F. Temporal requirement of Hoxa2 in cranial neural crest skeletal morphogenesis. Development. 2005;132:4927-36 pubmed..skeletal derivatives, reproducing the conventional Hoxa2 knockout phenotype, and induced rapid changes in Alx4, Bapx1, Six2 and Msx1 expression patterns...
- Kim T, Kim B, Mao J, Rowan S, Shivdasani R. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development. 2011;138:3225-33 pubmed publisher..These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth. ..
- Tucker A, Watson R, Lettice L, Yamada G, Hill R. Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution. Development. 2004;131:1235-45 pubmed..We show that, in combination with goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine middle ear...
- Chen X, Lufkin T. Linkage mapping of Sax2 to mouse chromosome 5. Mamm Genome. 1997;8:697-8 pubmed
- Stafford D, Brunet L, Khokha M, Economides A, Harland R. Cooperative activity of noggin and gremlin 1 in axial skeleton development. Development. 2011;138:1005-14 pubmed publisher..We conclude that Nog and Grem1 cooperate to maintain a BMP signaling-free zone that is a crucial prerequisite for Hh-mediated sclerotome induction...
- Brendolan A, Ferretti E, Salsi V, Moses K, Quaggin S, Blasi F, et al. A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Development. 2005;132:3113-26 pubmed..2 (Bapx1) and Pod1 (capsulin, Tcf21). We show that Hox11 and Nkx2...
- Burn S, Boot M, De Angelis C, Doohan R, Arques C, Torres M, et al. The dynamics of spleen morphogenesis. Dev Biol. 2008;318:303-11 pubmed publisher..Using a mouse line carrying a conditional Cre recombinase to mark early precursor cell populations, the spleen was found to derive from posterior mesenchyme distinct from the closely adjacent stomach mesenchyme. ..
- Rodrigo I, Hill R, Balling R, Munsterberg A, Imai K. Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development. 2003;130:473-82 pubmed..We show, by analyzing Pax1;Pax9 double mutant mice, that expression of Bapx1 in the sclerotome requires the presence of Pax1 and Pax9, in a gene dose-dependent manner...
- Aubin J, Déry U, Lemieux M, Chailler P, Jeannotte L. Stomach regional specification requires Hoxa5-driven mesenchymal-epithelial signaling. Development. 2002;129:4075-87 pubmed
- Skuntz S, Mankoo B, Nguyen M, Hustert E, Nakayama A, Tournier Lasserve E, et al. Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome polarity and leads to a remodeling of the cranio-cervical joints of the axial skeleton. Dev Biol. 2009;332:383-95 pubmed publisher..are associated with alterations in the expression of at least three transcription factor genes, Tbx18, Uncx, and Bapx1. As previously observed for Bapx1, MEOX1 protein occupies evolutionarily conserved promoter regions of Tbx18 and ..
- Coré N, Caubit X, Metchat A, Boned A, Djabali M, Fasano L. Tshz1 is required for axial skeleton, soft palate and middle ear development in mice. Dev Biol. 2007;308:407-20 pubmed..Finally, we demonstrate that Tshz1 is required for the development of the soft palate...
- Kobayashi T, Soegiarto D, Yang Y, Lanske B, Schipani E, McMahon A, et al. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest. 2005;115:1734-42 pubmed..These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP. ..
- Yoshiura K, Murray J. Sequence and chromosomal assignment of human BAPX1, a bagpipe-related gene, to 4p16.1: a candidate gene for skeletal dysplasia. Genomics. 1997;45:425-8 pubmed..Nkx-3.1 was isolated from the prostate, and its human homolog NKX-3.1 has also been described. Mouse Nkx-3.2, or bapx1, has also been isolated, and its expression in the visceral mesoderm and embryonic skeleton in the mouse has been ..
- Barrionuevo F, Taketo M, Scherer G, Kispert A. Sox9 is required for notochord maintenance in mice. Dev Biol. 2006;295:128-40 pubmed..Thus, Sox9 is required for axial skeletogenesis by regulating notochord survival and chondrogenesis. ..
- Wightman P, Hayward B, Bonthron D. The genes encoding glucokinase regulatory protein and ketohexokinase co-localize to mouse chromosome 5. Mamm Genome. 1997;8:700-1 pubmed
- Rodrigo I, Bovolenta P, Mankoo B, Imai K. Meox homeodomain proteins are required for Bapx1 expression in the sclerotome and activate its transcription by direct binding to its promoter. Mol Cell Biol. 2004;24:2757-66 pubmed..Genetic analysis has demonstrated that the transcription factors Pax1, Pax9, Meox1, Meox2, and Bapx1 are all required for sclerotomal differentiation. Their hierarchical relationship is, however, poorly understood...
- Jayewickreme C, Shivdasani R. Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1. Dev Biol. 2015;405:21-32 pubmed publisher..To determine these functions, we forced constitutive BARX1 expression in the Bapx1 expression domain, which includes the mesentery and intestinal mesenchyme, and also examined Barx1(-/)(-) embryos ..
- Champigny M, Mitchell M, Fox Robichaud A, Trigatti B, Igdoura S. A point mutation in the neu1 promoter recruits an ectopic repressor, Nkx3.2 and results in a mouse model of sialidase deficiency. Mol Genet Metab. 2009;97:43-52 pubmed publisher..Our findings support a significant role for lysosomal sialidase in inflammation and highlight the significance of repressor-recruitment in genetic disease. ..
- Landsman L, Nijagal A, Whitchurch T, Vanderlaan R, Zimmer W, MacKenzie T, et al. Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol. 2011;9:e1001143 pubmed publisher..These results have implications for developing strategies to expand pancreas progenitors and ?-cells for clinical transplantation. ..
- Kawato Y, Hirao M, Ebina K, Shi K, Hashimoto J, Honjo Y, et al. Nkx3.2 promotes primary chondrogenic differentiation by upregulating Col2a1 transcription. PLoS ONE. 2012;7:e34703 pubmed publisher..2 bound to the Col2a1 enhancer element. Nkx3.2 promoted primary chondrogenesis by two mechanisms: Direct and Sox9-independent upregulation of Col2a1 transcription and upregulation of Sox9 mRNA expression under positive feedback system. ..
- Behrens A, Haigh J, Mechta Grigoriou F, Nagy A, Yaniv M, Wagner E. Impaired intervertebral disc formation in the absence of Jun. Development. 2003;130:103-9 pubmed..Subsequently, fusion of vertebral bodies caused a scoliosis of the axial skeleton. Thus, Jun is required for axial skeletogenesis by regulating notochord survival and intervertebral disc formation. ..
- Tribioli C, Lufkin T. Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated Shh signaling in the developing limb. Dev Dyn. 2006;235:2483-92 pubmedTo explore Bapx1 homeobox gene function in embryonic control of development, we employed a gain-of-function approach to complement our previous loss-of-function mutant analysis...
- Kawato Y, Hirao M, Ebina K, Tamai N, Shi K, Hashimoto J, et al. Nkx3.2-induced suppression of Runx2 is a crucial mediator of hypoxia-dependent maintenance of chondrocyte phenotypes. Biochem Biophys Res Commun. 2011;416:205-10 pubmed publisher..These results demonstrated that Nkx3.2-dependent suppression of Runx2 was a crucial factor in hypoxia-dependent maintenance of chondrocyte identity. ..
- Zhang X, Ramalho Santos M, McMahon A. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell. 2001;105:781-92 pubmed..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.[Dedicated to Rosa Beddington, a pioneer in mammalian embryology]. ..
- Tanaka M, Kasahara H, Bartunkova S, Schinke M, Komuro I, Inagaki H, et al. Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in cardiovascular development. Dev Genet. 1998;22:239-49 pubmed..In this paper, we discuss molecular mechanisms of cardiovascular development with particular emphasis on roles of transcription factors. ..
- Cairns D, Liu R, Sen M, Canner J, Schindeler A, Little D, et al. Interplay of Nkx3.2, Sox9 and Pax3 regulates chondrogenic differentiation of muscle progenitor cells. PLoS ONE. 2012;7:e39642 pubmed publisher..Thus our in vitro and in vivo analyses suggest that the balance of Pax3, Nkx3.2 and Sox9 may act as a molecular switch during the chondrogenic differentiation of muscle progenitor cells, which may be important for fracture healing...
- Tavares A, Garcia E, Kuhn K, Woods C, Williams T, Clouthier D. Ectodermal-derived Endothelin1 is required for patterning the distal and intermediate domains of the mouse mandibular arch. Dev Biol. 2012;371:47-56 pubmed publisher..Together, our results illustrate an integral role for ectoderm-derived Edn1 in early arch morphogenesis, particularly in the intermediate domain...
- Herbrand H, Pabst O, Hill R, Arnold H. Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in sclerotomal development of the mouse. Mech Dev. 2002;117:217-24 pubmedThe homeobox containing transcription factors Nkx3.1 and Nkx3.2 (Bapx1) are transiently coexpressed in somites during early embryonic mouse development. Targeted disruption of the Nkx3...
- Zhang X, Ramalho Santos M, McMahon A. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell. 2001;106:781-92 pubmed..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis. ..
- Kim B, Miletich I, Mao J, McMahon A, Sharpe P, Shivdasani R. Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen. Development. 2007;134:3603-13 pubmed..These observations place Barx1 proximally within a Wt1 pathway of spleen development and reveal how a homeotic regulator employs different molecular mechanisms to mold neighboring organs. ..
- Park M, Yong Y, Choi S, Kim J, Lee J, Kim D. Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability. Nat Cell Biol. 2007;9:287-98 pubmed..Furthermore, we demonstrate that stage-specific NF-kappaB activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation. ..
- van Loenhout R, Tibboel D, Post M, Keijzer R. Congenital diaphragmatic hernia: comparison of animal models and relevance to the human situation. Neonatology. 2009;96:137-49 pubmed publisher..Several animal models have been proposed to study CDH. In this review we compare surgical, pharmacological and transgenic models, and discuss their strengths and limitations to study PH. ..
- Kuta A, Mao Y, Martin T, Ferreira de Sousa C, Whiting D, Zakaria S, et al. Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae. Development. 2016;143:2367-75 pubmed publisher..Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae. ..
- Bommireddy R, Ormsby I, Yin M, Boivin G, Babcock G, Doetschman T. TGF beta 1 inhibits Ca2+-calcineurin-mediated activation in thymocytes. J Immunol. 2003;170:3645-52 pubmed..Consequently, TGFbeta1 prevents autoimmune disease through a Ca(2+) regulatory pathway that maintains the activation threshold above that inducible by self-MHC-TCR interactions. ..
- Chan H, V S, Xing X, Kraus P, Yap S, Ng P, et al. Comparison of IRES and F2A-based locus-specific multicistronic expression in stable mouse lines. PLoS ONE. 2011;6:e28885 pubmed publisher..assess if EGFP was hindering the 'skipping' mechanism, we examined another mouse line co-expressing Bagpipe homeobox gene 1 homolog (Bapx1), Cre recombinase and EGFP (Bapx1(F2A-Cre-F2A-EGFP))...
- Kitazawa T, Takechi M, Hirasawa T, Adachi N, Narboux NÃªme N, Kume H, et al. Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids. Nat Commun. 2015;6:6853 pubmed publisher..We propose that differences in connection and release by various pharyngeal skeletal elements resulted in structural diversity, leading to the acquisition of the tympanic membrane in two distinct manners during amniote evolution. ..
- Takahashi Y, Takagi A, Hiraoka S, Koseki H, Kanno J, Rawls A, et al. Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation. Dev Dyn. 2007;236:1484-94 pubmed..By focusing on vertebral column formation, we found that expressions of Pax1, Nkx3.1, and Bapx1 are regulated by Paraxis and that Pax9 expression was severely affected in the Mesp2/Paraxis double-null embryo...
- Kim B, Woo J, Kanellopoulou C, Shivdasani R. Regulation of mouse stomach development and Barx1 expression by specific microRNAs. Development. 2011;138:1081-6 pubmed publisher..These results indicate that miRNAs are required for proper digestive tract organogenesis and that miR-7a and miR-203 control expression of the stomach homeotic regulator Barx1. ..