SIX2

Summary

Gene Symbol: SIX2
Description: SIX homeobox 2
Alias: homeobox protein SIX2, sine oculis homeobox homolog 2
Species: human
Products:     SIX2

Top Publications

  1. Jin M, Yin Z, Wei K, Xie Y, Bai X, Fu B, et al. Metanephric mesenchyme-derived Foxd1+ mesangial precursor cells alleviate mesangial proliferative glomerulonephritis. J Mol Med (Berl). 2019;: pubmed publisher
    ..The Foxd1+ cells showed the cell-specific expression of high levels of Foxd1 without Six2 and manifested specific cell surface markers of mesenchymal stem cells while retaining their differentiation ..
  2. Zheng L, Guo Q, Xiang C, Liu S, Jiang Y, Gao L, et al. Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells. J Hematol Oncol. 2019;12:23 pubmed publisher
    ..Transcriptional factor six2, CYP4Z1-3'UTR, and CYP4Z2P-3'UTR were stably overexpressed or knocked down in breast cancer cells via lentivirus ..
  3. Howden S, Vanslambrouck J, Wilson S, Tan K, Little M. Reporter-based fate mapping in human kidney organoids confirms nephron lineage relationships and reveals synchronous nephron formation. EMBO Rep. 2019;20: pubmed publisher
    ..Lineage tracing studies in mice identified a self-renewing Six2-expressing nephron progenitor population able to give rise to the full complement of nephrons throughout kidney ..
  4. Li S, Park J, Guan Y, Chung K, Shrestha R, Palmer M, et al. DNMT1 in Six2 Progenitor Cells Is Essential for Transposable Element Silencing and Kidney Development. J Am Soc Nephrol. 2019;30:594-609 pubmed publisher
    ..and Ten-eleven translocation methylcytosine hydroxylases (Tet2) in nephron progenitor cells (Six2 Cre) in mice...
  5. Li Z, Araoka T, Belmonte J. Gene Editing in 3D Cultured Nephron Progenitor Cell Lines. Methods Mol Biol. 2019;1926:151-159 pubmed publisher
    During kidney development, Six2+ nephron progenitor cells (NPCs) generate nephrons, the functional units of the kidney. Isolating and expanding NPCs in vitro have enabled wide applications in both basic and translational research...
  6. Oliphant M, Vincent M, Galbraith M, Pandey A, Zaberezhnyy V, Rudra P, et al. SIX2 Mediates Late-Stage Metastasis via Direct Regulation of SOX2 and Induction of a Cancer Stem Cell Program. Cancer Res. 2019;79:720-734 pubmed publisher
    ..Here we identify Six2, a developmental transcription factor, as a critical regulator of a breast cancer stem cell program that enables ..
  7. Minocha E, Chaturvedi C, Nityanand S. Renogenic characterization and in vitro differentiation of rat amniotic fluid stem cells into renal proximal tubular- and juxtaglomerular-like cells. In Vitro Cell Dev Biol Anim. 2019;55:138-147 pubmed publisher
    ..cells and expressed mesenchymal markers CD73, CD90, and CD105 as well as renal progenitor markers WT1, PAX2, SIX2, SALL1, and CITED1...
  8. Hiratsuka K, Monkawa T, Akiyama T, Nakatake Y, Oda M, Goparaju S, et al. Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors. Sci Rep. 2019;9:913 pubmed publisher
    ..The first set - FIGLA, PITX2, ASCL1 and TFAP2C, differentiated hPSCs into SIX2+SALL1+ nephron progenitor cells with 92% efficiency within 2 days...
  9. Nishikawa M, Yuri S, Kimura H, Yanagawa N, Hamon M, Hauser P, et al. Comprehensive analysis of chromatin signature and transcriptome uncovers functional lncRNAs expressed in nephron progenitor cells. Biochim Biophys Acta Gene Regul Mech. 2018;1862:58-70 pubmed publisher
    ..Out of these MM specific lncRNAs, we identified a lncRNA, Gm29418, in a distal enhancer region of Six2, a key regulatory gene of MM cells...

More Information

Publications101 found, 100 shown here

  1. Bonventre J. Kidney organoids-a new tool for kidney therapeutic development. Kidney Int. 2018;94:1040-1042 pubmed publisher
    ..Boreström et al. have used CRISPR/Cas9 to create kidney fluorescent lineage markers for SIX2 and NPHS1 to monitor the differentiation process to tubular and glomerular structures and optimize maturity...
  2. Ide S, Finer G, Maezawa Y, Onay T, Souma T, Scott R, et al. Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development. J Am Soc Nephrol. 2018;29:2795-2808 pubmed publisher
    ..Transcription factor 21 (Tcf21) is highly expressed in the metanephric mesenchyme, including Six2-expressing cap mesenchyme and Foxd1-expressing stromal mesenchyme...
  3. Yallowitz A, Gong K, Swinehart I, Nelson L, Wellik D. Non-homeodomain regions of Hox proteins mediate activation versus repression of Six2 via a single enhancer site in vivo. Dev Biol. 2009;335:156-65 pubmed publisher
    ..b>Six2 is genetically downstream of both the Hox11 paralogous genes in the developing mammalian kidney and Hoxa2 in ..
  4. Nagalakshmi V, Li M, Shah S, Gigliotti J, Klibanov A, Epstein F, et al. Changes in cell fate determine the regenerative and functional capacity of the developing kidney before and after release of obstruction. Clin Sci (Lond). 2018;132:2519-2545 pubmed publisher
    ..Degeneration of Sine Oculis Homeobox Homolog 2 (Six2) and HoxB7-derived cells resulted in significant loss of glomeruli, nephron tubules, and ..
  5. Toka H, Al Romaih K, Koshy J, Dibartolo S, Kos C, Quinn S, et al. Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone-independent hypocalciuria. J Am Soc Nephrol. 2012;23:1879-90 pubmed publisher
    ..Using animals expressing Cre recombinase driven by the Six2 promoter, we generated mice that appeared grossly normal but had undetectable levels of Casr mRNA and protein in ..
  6. Hariharan K, Stachelscheid H, Rossbach B, Oh S, Mah N, Schmidt Ott K, et al. Parallel generation of easily selectable multiple nephronal cell types from human pluripotent stem cells. Cell Mol Life Sci. 2019;76:179-192 pubmed publisher
    ..BMP4, and Retinoic acid followed by GDNF, which steered hPSCs to the renal lineage and resulted in populations of SIX2+/CITED1+ metanephric mesenchyme- (MM) and of HOXB7+/GRHL2+ ureteric bud ..
  7. Li J, Huang C, Li J, Yuan J, Chen Q, Zhang W, et al. Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in hepatocellular carcinoma cells. Biomed Pharmacother. 2018;104:204-210 pubmed publisher
    This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival...
  8. He Q, Chen L, Liu Y, Wu Y, Ni D, Liu J, et al. Gulo regulates the proliferation, apoptosis and mesenchymal-to-epithelial transformation of metanephric mesenchyme cells via inhibiting Six2. Biochem Biophys Res Commun. 2018;504:885-891 pubmed publisher
    ..and differentiation of metanephric mesenchyme (MM) cells, mainly regulated by Sine oculis-related homeobox 2 (Six2), is critical for forming mature kidney...
  9. Li Y, Liu J, Li W, Brown A, Baddoo M, Li M, et al. p53 Enables metabolic fitness and self-renewal of nephron progenitor cells. Development. 2015;142:1228-41 pubmed publisher
    ..deletion of p53 in nephron progenitor cells (Six2Cre(+);p53(fl/fl)) induces progressive depletion of Cited1(+)/Six2(+) self-renewing progenitors and loss of cap mesenchyme (CM) integrity...
  10. Rabadi M, Abdulmahdi W, Nesi L, Jules E, Marghani Y, Sheinin E, et al. Maternal malnourishment induced upregulation of fetuin-B blunts nephrogenesis in the low birth weight neonate. Dev Biol. 2018;443:78-91 pubmed publisher
    ..For reasons unknown, these LBW neonates have impaired kidney development due to a severe reduction in renal SIX2+ stem cells during nephrogenesis...
  11. Pierce J, Murphy A, Panzer A, de Caestecker C, Ayers G, Neblett D, et al. SIX2 Effects on Wilms Tumor Biology. Transl Oncol. 2014;7:800-11 pubmed publisher
    ..Sine oculis homeobox 2 (SIX2) is a transcription factor expressed specifically in the CM, provides a critical mechanism for CM self-renewal, and ..
  12. Nagy I, Xu Q, Naillat F, Ali N, Miinalainen I, Samoylenko A, et al. Impairment of Wnt11 function leads to kidney tubular abnormalities and secondary glomerular cystogenesis. BMC Dev Biol. 2016;16:30 pubmed publisher
    ..failure of Wnt11 signaling reduced the expression of several genes implicated in kidney development, such as Wnt9b, Six2, Foxd1 and Hox10...
  13. Kobayashi A, Mugford J, Krautzberger A, Naiman N, Liao J, McMahon A. Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis. Stem Cell Reports. 2014;3:650-62 pubmed publisher
    The mammalian kidney is a complex organ consisting of multiple cell types. We previously showed that the Six2-expressing cap mesenchyme is a multipotent self-renewing progenitor population for the main body of the nephron, the basic ..
  14. Boreström C, Jonebring A, Guo J, Palmgren H, Cederblad L, Forslöw A, et al. A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell-derived kidney model for drug discovery. Kidney Int. 2018;94:1099-1110 pubmed publisher
    ..podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1)...
  15. Xu J, Wong E, Cheng C, Li J, Sharkar M, Xu C, et al. Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis. Dev Cell. 2014;31:434-47 pubmed publisher
    ..Here we show that Eya1 interacts with Six2 and Myc to control self-renewing cell activity...
  16. Morizane R, Lam A, Freedman B, Kishi S, Valerius M, Bonventre J. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol. 2015;33:1193-200 pubmed
    ..By recapitulating metanephric kidney development in vitro, we generate SIX2+ SALL1+ WT1+ PAX2+ NPCs with 90% efficiency within 9 days of differentiation...
  17. Rahman M, Spitzhorn L, Wruck W, Hagenbeck C, Balan P, Graffmann N, et al. The presence of human mesenchymal stem cells of renal origin in amniotic fluid increases with gestational time. Stem Cell Res Ther. 2018;9:113 pubmed publisher
    ..AF-MSCs expressed the master renal progenitor markers SIX2 and CITED1, in addition to typical renal proteins such as PODXL, LHX1, BRN1 and PAX8...
  18. Wang C, Drasin D, Pham C, Jedlicka P, Zaberezhnyy V, Guney M, et al. Homeoprotein Six2 promotes breast cancer metastasis via transcriptional and epigenetic control of E-cadherin expression. Cancer Res. 2014;74:7357-70 pubmed publisher
    ..In this study, we report the involvement of the kidney development transcription factor Six2 in the metastatic progression of human breast cancer...
  19. Bagherie Lachidan M, Reginensi A, Pan Q, Zaveri H, Scott D, Blencowe B, et al. Stromal Fat4 acts non-autonomously with Dchs1/2 to restrict the nephron progenitor pool. Development. 2015;142:2564-73 pubmed publisher
    ..Analysis of Six2(-/-);Fat4(-/-) double mutants demonstrates that excess progenitors in Fat4 mutants are dependent on Six2, a crucial ..
  20. Wada S, Ideno H, Shimada A, Kamiunten T, Nakamura Y, Nakashima K, et al. H3K9MTase G9a is essential for the differentiation and growth of tenocytes in vitro. Histochem Cell Biol. 2015;144:13-20 pubmed publisher
    ..e., Scleraxis (Scx), Mohawk (Mkx), Egr1, Six1, and Six2 were all suppressed in G9a-null tenocytes...
  21. Liu H, Chen S, Yao X, Li Y, Chen C, Liu J, et al. Histone deacetylases 1 and 2 regulate the transcriptional programs of nephron progenitors and renal vesicles. Development. 2018;145: pubmed publisher
    Nephron progenitor cells (NPCs) are Six2-positive metanephric mesenchyme cells, which undergo self-renewal and differentiation to give rise to nephrons until the end of nephrogenesis...
  22. Hoshina A, Kawamoto T, Sueta S, Mae S, Araoka T, Tanaka H, et al. Development of new method to enrich human iPSC-derived renal progenitors using cell surface markers. Sci Rep. 2018;8:6375 pubmed publisher
    ..markers, CD9-CD140a+CD140b+CD271+, which could enrich OSR1+SIX2+ renal progenitors...
  23. He G, Tavella S, Hanley K, Self M, Oliver G, Grifone R, et al. Inactivation of Six2 in mouse identifies a novel genetic mechanism controlling development and growth of the cranial base. Dev Biol. 2010;344:720-30 pubmed publisher
    ..Here, we describe a novel and specific role for the homeoprotein Six2 in the growth and elongation of the cranial base...
  24. Lv X, Mao Z, Lyu Z, Zhang P, Zhan A, Wang J, et al. miR181c promotes apoptosis and suppresses proliferation of metanephric mesenchyme cells by targeting Six2 in vitro. Cell Biochem Funct. 2014;32:571-9 pubmed publisher
    ..In our study, we aimed to explore the regulation role of miR181c towards Six2 in metanephric mesenchyme (MM) cells...
  25. Song R, Kidd L, Janssen A, Yosypiv I. Conditional ablation of the prorenin receptor in nephron progenitor cells results in developmental programming of hypertension. Physiol Rep. 2018;6:e13644 pubmed publisher
    ..Previously, we demonstrated that conditional ablation of the PRR in Six2+ NPCs in mice (Six2PRR-/- ) causes early neonatal death...
  26. Phelps H, Al Jadiry M, Corbitt N, Pierce J, Li B, Wei Q, et al. Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq. World J Pediatr. 2018;14:585-593 pubmed publisher
    ..of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed...
  27. Wang S, Gu Y, Wolff N, Stefanius K, Christie A, Dey A, et al. Bap1 is essential for kidney function and cooperates with Vhl in renal tumorigenesis. Proc Natl Acad Sci U S A. 2014;111:16538-43 pubmed publisher
    ..b>Six2-Cre;Vhl(F/F);Bap1(F/+) mice developed ccRCC, but Six2-Cre;Vhl(F/F) mice did not...
  28. Nishikawa M, Kimura H, Yanagawa N, Hamon M, Hauser P, Zhao L, et al. An optimal serum-free defined condition for in vitro culture of kidney organoids. Biochem Biophys Res Commun. 2018;501:996-1002 pubmed publisher
    ..found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2+ nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis...
  29. Hsieh W, Ramadesikan S, FEKETE D, Aguilar R. Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex. PLoS ONE. 2018;13:e0192635 pubmed publisher
    ..Additionally, the transcription factor and cap mesenchyme marker Six2 was substantially retained in the Golgi complex and the functional nuclear-localized fraction was reduced...
  30. Hwang D, Kohl S, Fan X, Vivante A, Chan S, Dworschak G, et al. Mutations of the SLIT2-ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract. Hum Genet. 2015;134:905-16 pubmed publisher
    ..We show that SRGAP1 is expressed in early mouse nephrogenic mesenchyme and that it is coexpressed with ROBO2 in SIX2-positive nephron progenitor cells of the cap mesenchyme in developing rat kidney...
  31. Tanigawa S, Sharma N, Hall M, Nishinakamura R, Perantoni A. Preferential Propagation of Competent SIX2+ Nephronic Progenitors by LIF/ROCKi Treatment of the Metanephric Mesenchyme. Stem Cell Reports. 2015;5:435-47 pubmed publisher
    ..Accordingly, we established a culture model that preferentially expands the MM SIX2+ progenitor pool using leukemia inhibitory factor (LIF), a Rho kinase inhibitor (ROCKi), and extracellular matrix...
  32. Tanigawa S, Perantoni A. Modeling renal progenitors - defining the niche. Differentiation. 2016;91:152-8 pubmed publisher
    ..mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+progenitor.
  33. Xu J, Liu H, Chai O, Lan Y, Jiang R. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis. PLoS ONE. 2016;11:e0159597 pubmed publisher
    ..the metanephric mesenchyme, with the Osr1+/-Wt1+/- mouse embryos exhibiting significantly reduced Pax2-positive and Six2-positive nephron progenitor cells...
  34. Toyohara T, Mae S, Sueta S, Inoue T, Yamagishi Y, Kawamoto T, et al. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice. Stem Cells Transl Med. 2015;4:980-92 pubmed publisher
    ..We established a multistep differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and ..
  35. Liu J, Ju P, Zhou Y, Zhao Y, Xie Y, Long Y, et al. Six2 Is a Coordinator of LiCl-Induced Cell Proliferation and Apoptosis. Int J Mol Sci. 2016;17: pubmed publisher
    ..b>Six2, a biological marker related to Wnt signaling pathway, promotes the proliferation, inhibits the apoptosis and ..
  36. Chung E, Deacon P, Marable S, Shin J, Park J. Notch signaling promotes nephrogenesis by downregulating Six2. Development. 2016;143:3907-3913 pubmed
    ..We show in mice that differentiation of nephron progenitors requires downregulation of Six2, a transcription factor required for progenitor maintenance, and that Notch signaling is necessary and sufficient ..
  37. Zhou Z, Wang J, Guo C, Chang W, Zhuang J, Zhu P, et al. Temporally Distinct Six2-Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease. Cell Rep. 2017;18:1019-1032 pubmed publisher
    The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors...
  38. Lindström N, Guo J, Kim A, TRAN T, Guo Q, De Sena Brandine G, et al. Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney. J Am Soc Nephrol. 2018;29:806-824 pubmed publisher
    ..In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely ..
  39. Pode Shakked N, Pleniceanu O, Gershon R, Shukrun R, Kanter I, Bucris E, et al. Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells. Sci Rep. 2016;6:23562 pubmed publisher
    ..a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1(+)CD133(-) marks SIX2(+) multipotent renal stem cells transiting to NCAM1(+)CD133(+) differentiating segment-specific SIX2(-) epithelial ..
  40. Shukuya K, Ogura S, Tokuhara Y, Okubo S, Yatomi Y, Tozuka M, et al. Novel round cells in urine sediment and their clinical implications. Clin Chim Acta. 2016;457:142-9 pubmed publisher
    ..Also it was positive for undifferentiated cell markers, including PAX2, WT1, OSR1, and SIX2. They were observed in end-stage renal failure patients and the number of cells was correlated with the severity of ..
  41. Suzuki N, Hirano K, Ogino H, Ochi H. Identification of distal enhancers for Six2 expression in pronephros. Int J Dev Biol. 2015;59:241-6 pubmed publisher
    The embryonic nephric mesenchyme contains pluripotent progenitor cells. Six2, a homeodomain transcription factor, is expressed in a subset of the nephric mesenchyme, and it functions to maintain a progenitor state by suppressing ..
  42. Noizet M, Lagoutte E, Gratigny M, Bouschbacher M, Lazareth I, Roest Crollius H, et al. Master regulators in primary skin fibroblast fate reprogramming in a human ex vivo model of chronic wounds. Wound Repair Regen. 2016;24:247-62 pubmed publisher
    ..Conversely, down-regulation of MEOX2, SIX2, and MAF causes reprogramming of fibroblasts to myofibroblasts even in absence of TGF-β, the natural inducer of ..
  43. Arda H, Li L, Tsai J, Torre E, Rosli Y, Peiris H, et al. Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human ? Cell Function. Cell Metab. 2016;23:909-20 pubmed publisher
    ..Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia ..
  44. Georgas K, Rumballe B, Valerius M, Chiu H, Thiagarajan R, Lesieur E, et al. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev Biol. 2009;332:273-86 pubmed publisher
    ..Using Six2-eGFPCre x R26R-lacZ mice, we demonstrate that these cells are derived from the cap mesenchyme and not the ureteric ..
  45. Monteiro Carvalho Mori da Cunha M, Zia S, Oliveira Arcolino F, Carlon M, Beckmann D, Pippi N, et al. Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats. PLoS ONE. 2015;10:e0136145 pubmed publisher
    ..In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized...
  46. Gao J, Kang X, Sun S, Li L, Zhang B, Li Y, et al. Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression. Cell Death Dis. 2016;7:e2217 pubmed publisher
    ..In this study, we found that the expression level of transcription factor Six2 was increased in damaged DA neurons after GDNF rescue in vivo and in vitro...
  47. Xu Y, Zhou T, Shao L, Zhang B, Liu K, Gao C, et al. Gene expression profiles in mouse cumulus cells derived from in vitro matured oocytes with and without blastocyst formation. Gene Expr Patterns. 2017;25-26:46-58 pubmed publisher
    ..transcripts after comparison with the reference group: Arrb1, Atp2c1, Cdh5, Cntnap1, Mkln1, Lgr4, Rhobtb1, Smc2 and Six2, as the candidate target genes...
  48. Blake J, Hu D, Cain J, Rosenblum N. Urogenital development in Pallister-Hall syndrome is disrupted in a cell-lineage-specific manner by constitutive expression of GLI3 repressor. Hum Mol Genet. 2016;25:437-47 pubmed publisher
    ..In the ureteric bud, GLI3R expression decreased branching morphogenesis. In Six2-positive nephrogenic progenitors, GLI3R decreased progenitor cell proliferation reducing the number of nephrogenic ..
  49. Zhu S, Chen C, Jiang Z, Yuan B, Ji M, Wu F, et al. MicroRNA-185 inhibits cell proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Six2. Eur Rev Med Pharmacol Sci. 2016;20:1712-9 pubmed
    ..Real-time PCR was used to measure the mRNA expression of miR-185 and Six2. In addition, protein expression levels of Six2 and EMT-related markers were determined by western blot...
  50. O Brien L, Guo Q, Bahrami Samani E, Park J, Hasso S, Lee Y, et al. Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies. PLoS Genet. 2018;14:e1007181 pubmed publisher
    ..Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron ..
  51. Song R, Preston G, Kidd L, Bushnell D, Sims Lucas S, Bates C, et al. Prorenin receptor is critical for nephron progenitors. Dev Biol. 2016;409:382-91 pubmed publisher
    ..potential role of the PRR in nephrogenesis, we generated a mouse model with a conditional deletion of the PRR in Six2(+) nephron progenitors and their epithelial derivatives (Six2(PRR-/-))...
  52. Spreafico F, Ciceri S, Gamba B, Torri F, Terenziani M, Collini P, et al. Chromosomal anomalies at 1q, 3, 16q, and mutations of SIX1 and DROSHA genes underlie Wilms tumor recurrences. Oncotarget. 2016;7:8908-15 pubmed publisher
    ..primary/recurrent WTs through whole-genome SNP arrays, and investigated known WT-associated genes, including SIX1, SIX2 and micro RNA processor genes, whose mutations have been recently proposed as associated with worse outcome...
  53. Camarata T, Howard A, Elsey R, Raza S, O Connor A, Beatty B, et al. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney. PLoS ONE. 2016;11:e0153422 pubmed publisher
    ..carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends...
  54. Kirita Y, Kami D, Ishida R, Adachi T, Tamagaki K, Matoba S, et al. Preserved Nephrogenesis Following Partial Nephrectomy in Early Neonates. Sci Rep. 2016;6:26792 pubmed publisher
    ..During normal development, Six2 expression and Six2+ nephron progenitor cells in the cap mesenchyme both rapidly disappear after birth...
  55. Gu Y, Zhao Y, Zhou Y, Xie Y, Ju P, Long Y, et al. Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells. Int J Mol Sci. 2016;17: pubmed publisher
    ..Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney...
  56. 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
    ..ectopically in BARX1(+) intestinal mesenchyme and reduced in Barx1(-/-) stomach mesenchyme include Isl1, Pitx1, Six2 and Pitx2, transcription factors known to control left-right patterning and influence smooth muscle development...
  57. Yuri S, Nishikawa M, Yanagawa N, Jo O, Yanagawa N. Maintenance of Mouse Nephron Progenitor Cells in Aggregates with Gamma-Secretase Inhibitor. PLoS ONE. 2015;10:e0129242 pubmed publisher
    ..We found that Six2-expressing (Six2(+))-NPC could be maintained in aggregates reconstituted with dispersed cells from E12...
  58. Celli J, van Beusekom E, Hennekam R, Gallardo M, Smeets D, de Cordoba S, et al. Familial syndromic esophageal atresia maps to 2p23-p24. Am J Hum Genet. 2000;66:436-44 pubmed
    ..3 cM in the 2p23-p24 region. These results show that haploinsufficiency for a gene or genes in 2p23-p24 is associated with syndromic EA. ..
  59. Hwang J, Sim X, Wu Y, Liang J, Tabara Y, Hu C, et al. Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. Diabetes. 2015;64:291-8 pubmed publisher
    ..Our results could provide additional insight into the genetic variation implicated in fasting glucose regulation. ..
  60. Naiman N, Fujioka K, Fujino M, Valerius M, Potter S, McMahon A, et al. Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary during Kidney Development. Dev Cell. 2017;41:349-365.e3 pubmed publisher
    ..Previously we discovered that, once Six2-expressing nephron progenitor cells and Foxd1-expressing renal interstitial progenitor cells form at the onset of ..
  61. Monks D, Jahangir A, Shanske A, Samanich J, Morrow B, Babcock M. Mutational analysis of HOXA2 and SIX2 in a Bronx population with isolated microtia. Int J Pediatr Otorhinolaryngol. 2010;74:878-82 pubmed publisher
    ..Mutations in the homeobox gene HOXA2 caused microtia in a single Iranian family. Another homeobox gene, SIX2, acts downstream of HOXA2 during development and provides another possible candidate for mutational analysis...
  62. Liu Q, Li A, Tian Y, Liu Y, Li T, Zhang C, et al. The expression profile and clinic significance of the SIX family in non-small cell lung cancer. J Hematol Oncol. 2016;9:119 pubmed
    ..SIX4 and SIX6 were linked to the lymph node metastasis (LNM). SIX2, SIX3, and SIX4 were correlated with higher TNM stages...
  63. Wu D, Lin P, Wang L, Huang C, Lee H. The YAP1/SIX2 axis is required for DDX3-mediated tumor aggressiveness and cetuximab resistance in KRAS-wild-type colorectal cancer. Theranostics. 2017;7:1114-1132 pubmed publisher
    ..DDX3-mediated aggressiveness and CTX resistance were regulated by the YAP1/SIX2 axis in KRAS-WT cells and further confirmed in animal models...
  64. Kumar J. The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease. Cell Mol Life Sci. 2009;66:565-83 pubmed publisher
  65. Hufnagel R, Zimmerman S, Krueger L, Bender P, Ahmed Z, Saal H. A new frontonasal dysplasia syndrome associated with deletion of the SIX2 gene. Am J Med Genet A. 2016;170A:487-491 pubmed publisher
    ..3 kilobase deletion of chromosome 2p21 segregating with phenotype and limited to the sine oculis homeobox gene SIX2 and surrounding noncoding DNA...
  66. Xia H, Yan X, Liu Y, Ju P, Liu J, Ni D, et al. Six2 is involved in GATA1-mediated cell apoptosis in mouse embryonic kidney-derived cell lines. In Vitro Cell Dev Biol Anim. 2017;53:827-833 pubmed publisher
    b>Six2 (Sine oculis homeobox 2), a homeodomain transcription factor, plays a crucial role in the regulation of mammalian nephrogenesis...
  67. Yamanaka S, Tajiri S, Fujimoto T, Matsumoto K, Fukunaga S, Kim B, et al. Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system. Nat Commun. 2017;8:1719 pubmed publisher
    ..We successfully achieved removal of Six2+ NPCs within the nephrogenic niche and complete replacement of transplanted NPCs with donor cells...
  68. Buller C, Xu X, Marquis V, Schwanke R, Xu P. Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome. Hum Mol Genet. 2001;10:2775-81 pubmed
    ..However, four mutations are crucial for protein-protein interactions in both yeast and mammalian cells. Our results provide insights into the molecular mechanisms of organ defects detected in human syndromes. ..
  69. Senanayake U, Koller K, Pichler M, Leuschner I, Strohmaier H, Hadler U, et al. The pluripotent renal stem cell regulator SIX2 is activated in renal neoplasms and influences cellular proliferation and migration. Hum Pathol. 2013;44:336-45 pubmed publisher
    Embryonal renal mesenchyme contains pluripotent progenitor cells characterized by expression of SIX2, which suppresses cellular differentiation...
  70. Okello D, Iyyanar P, Kulyk W, Smith T, Lozanoff S, Ji S, et al. Six2 Plays an Intrinsic Role in Regulating Proliferation of Mesenchymal Cells in the Developing Palate. Front Physiol. 2017;8:955 pubmed publisher
    ..The Sine oculis-related homeobox 2 (Six2) gene has been linked to abnormalities of craniofacial and kidney development...
  71. Kawakami K, Ohto H, Takizawa T, Saito T. Identification and expression of six family genes in mouse retina. FEBS Lett. 1996;393:259-63 pubmed
    We identified five cDNA clones of the Six gene family which are expressed in retina. They are Six2, Six3 alpha and Six3 beta (which are derived from alternative splicing forms), Six5, and AREC3/Six4...
  72. L pez R os J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P. Six3 and Six6 activity is modulated by members of the groucho family. Development. 2003;130:185-95 pubmed
    ..These data indicate that both Tle1 and Aes participate in the molecular network that control eye development and are consistent with the view that both Six3 and Six6 act in combination with either Tle1 and/or Aes...
  73. Wegert J, Ishaque N, Vardapour R, Geörg C, Gu Z, Bieg M, et al. Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors. Cancer Cell. 2015;27:298-311 pubmed publisher
    ..Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18...
  74. Song D, Yue L, Wu G, Ma S, Guo L, Yang H, et al. Assessment of promoter methylation and expression of SIX2 as a diagnostic and prognostic biomarker in Wilms' tumor. Tumour Biol. 2015;36:7591-8 pubmed publisher
    This study was designed to evaluate the utility of expression and DNA methylation patterns of the sine oculis homeobox homolog 2 (SIX2) gene in early diagnosis and prognosis of Wilms' tumor (WT)...
  75. Hachiya T, Komaki S, Hasegawa Y, Ohmomo H, Tanno K, Hozawa A, et al. Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA1c. Sci Rep. 2017;7:16147 pubmed publisher
    ..3 × 10-20) and SIX3-SIX2 (P = 8.6 × 10-9)...
  76. Weber S, Taylor J, Winyard P, Baker K, Sullivan Brown J, Schild R, et al. SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol. 2008;19:891-903 pubmed publisher
    ..Here, we report the first mutations in BMP4 and SIX2 identified in patients with RHD...
  77. Christensen K, Patrick A, McCoy E, Ford H. The six family of homeobox genes in development and cancer. Adv Cancer Res. 2008;101:93-126 pubmed publisher
    ..Emerging evidence for the importance of Six family members and their cofactors in numerous human tumors suggests that targeting of this complex may be a novel and powerful means to inhibit both tumor growth and progression. ..
  78. Walz A, Ooms A, Gadd S, Gerhard D, Smith M, Guidry Auvil J, et al. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer Cell. 2015;27:286-97 pubmed publisher
    ..The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death. ..
  79. O Brien L, Guo Q, Lee Y, TRAN T, Bénazet J, Whitney P, et al. Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators. Development. 2016;143:595-608 pubmed publisher
    ..In the mouse, the related transcriptional regulators Six1 and Six2 play non-overlapping roles in nephron progenitors...
  80. Bohndorf M, Ncube A, Spitzhorn L, Enczmann J, Wruck W, Adjaye J. Derivation and characterization of integration-free iPSC line ISRM-UM51 derived from SIX2-positive renal cells isolated from urine of an African male expressing the CYP2D6 *4/*17 variant which confers intermediate drug metabolizing activity. Stem Cell Res. 2017;25:18-21 pubmed publisher
    b>SIX2-positive renal cells isolated from urine from a 51year old male of African origin bearing the CYP2D6 *4/*17 variant were reprogrammed by nucleofection of a combination of two episomal-based plasmids omitting pathway (TGF?, MEK and ..
  81. Combes A, Wilson S, Phipson B, Binnie B, Ju A, Lawlor K, et al. Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number. Kidney Int. 2018;93:589-598 pubmed publisher
    ..Transcription factors within this progenitor population, such as SIX2, are assumed to control expression of genes promoting self-renewal such that homozygous Six2 deletion results in ..
  82. Murphy A, Pierce J, de Caestecker C, Taylor C, Anderson J, Perantoni A, et al. SIX2 and CITED1, markers of nephronic progenitor self-renewal, remain active in primitive elements of Wilms' tumor. J Pediatr Surg. 2012;47:1239-49 pubmed publisher
    b>SIX2 and CITED1 are transcriptional regulators that specify self-renewing nephronic progenitor cells of the embryonic kidney...
  83. Guan J, Wang D, Cao W, Zhao Y, Du R, Yuan H, et al. SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans. J Hum Genet. 2016;61:917-922 pubmed publisher
    ..We confirmed the presence of a novel 60?kb heterozygous deletion in size, encompassing SIX2 in our family...
  84. Mao Z, Lyu Z, Huang L, Zhou Q, Weng Y. T?RII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2 In Vitro. Int J Mol Sci. 2017;18: pubmed publisher
    ..role of TGF? type II receptor (T?RII) in vitro, which has a similar expression pattern as the crucial regulator Six2 during early kidney development...
  85. Van Dam P, Rep M. The Distribution of Miniature Impala Elements and SIX Genes in the Fusarium Genus is Suggestive of Horizontal Gene Transfer. J Mol Evol. 2017;85:14-25 pubmed publisher
    ..oxysporum f. sp. hyacinthi and f. sp. lilii. The Fo f. sp. lycopersici SIX2 effector gene was found to be widely distributed (15/18 isolates) throughout the F...
  86. Rasouly H, Kumar S, Chan S, Pisarek Horowitz A, Sharma R, Xi Q, et al. Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease. Kidney Int. 2016;90:1262-1273 pubmed publisher
    ..Here we show that deletion of Zeb2 in mesenchyme-derived nephrons with either Pax2-cre or Six2-cre causes primary glomerulocystic kidney disease without tubular cysts in mice...
  87. Davies J. Pax2: A "Keep to the Path" Sign on Waddington's Epigenetic Landscape. Dev Cell. 2017;41:331-332 pubmed publisher
    Developing kidneys have Foxd1+ stromogenic stem cells and [Six2+, Pax2+] nephrogenic stem cells. In this issue of Developmental Cell, Naiman et al...
  88. Basta J, Robbins L, Denner D, Kolar G, Rauchman M. A Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation. Development. 2017;144:3080-3094 pubmed publisher
    ..These findings highlight an important function of Sall1-NuRD interaction in the regulation of Six2-positive multipotent renal progenitor cells and formation of the loop of Henle.
  89. Magella B, Adam M, Potter A, Venkatasubramanian M, Chetal K, Hay S, et al. Cross-platform single cell analysis of kidney development shows stromal cells express Gdnf. Dev Biol. 2018;434:36-47 pubmed publisher
    ..cells was validated in several ways, including Gdnf in situ hybridization combined with immunohistochemistry for SIX2, and marker of nephron progenitors, and MEIS1, a marker of stromal cells...
  90. Boucher C, Winchester C, Hamilton G, Winter A, Johnson K, Bailey M. Structure, mapping and expression of the human gene encoding the homeodomain protein, SIX2. Gene. 2000;247:145-51 pubmed
    ..We have cloned and characterised the gene that encodes human SIX2, elucidated its gene structure and conducted expression studies in a range of tissues...
  91. Ikeda K, Watanabe Y, Ohto H, Kawakami K. Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol Cell Biol. 2002;22:6759-66 pubmed
    ..This work provides fundamental information on the role and the mechanism of action of this gene cassette in tissue differentiation and organogenesis. ..
  92. Gadd S, Huff V, Walz A, Ooms A, Armstrong A, Gerhard D, et al. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat Genet. 2017;49:1487-1494 pubmed publisher
    ..In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in ..