Gene Symbol: Eya1
Description: EYA transcriptional coactivator and phosphatase 1
Alias: bor, eyes absent homolog 1, eyes absent 1 homolog
Species: mouse
Products:     Eya1

Top Publications

  1. Sajithlal G, Zou D, Silvius D, Xu P. Eya 1 acts as a critical regulator for specifying the metanephric mesenchyme. Dev Biol. 2005;284:323-36 pubmed
  2. Xu P, Woo I, Her H, Beier D, Maas R. Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode. Development. 1997;124:219-31 pubmed
    We have identified and mapped three members of a new family of vertebrate genes, designated Eya1, Eya2 and Eya3, which share high sequence similarity with the Drosophila eyes absent (eya) gene...
  3. Zou D, Silvius D, Rodrigo Blomqvist S, Enerback S, Xu P. Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear. Dev Biol. 2006;298:430-41 pubmed
    ..While mutations in human EYA4 cause late-onset deafness at the DFNA10 locus, mutations in human EYA1 cause branchio-oto-renal (BOR) syndrome...
  4. Musharraf A, Markschies N, Teichmann K, Pankratz S, Landgraf K, Englert C, et al. Eyes absent proteins: characterization of substrate specificity and phosphatase activity of mutants associated with branchial, otic and renal anomalies. Chembiochem. 2008;9:2285-94 pubmed publisher
    ..In addition, we analysed the phosphatase activity of a number of variants of the mouse Eya1 protein that harbours single point mutations that were associated with branchio-oto-renal syndrome (BOR), branchio-..
  5. Rayapureddi J, Kattamuri C, Steinmetz B, Frankfort B, Ostrin E, Mardon G, et al. Eyes absent represents a class of protein tyrosine phosphatases. Nature. 2003;426:295-8 pubmed
    ..Furthermore, the phosphatase activity of Eyes absent contributes to its ability to induce eye formation in Drosophila. ..
  6. Xu P, Cheng J, Epstein J, Maas R. Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function. Proc Natl Acad Sci U S A. 1997;94:11974-9 pubmed
    ..Here we show that Eya1 and Eya2, two mouse homologues of Drosophila eya, are expressed initially during limb development in connective ..
  7. Gong K, Yallowitz A, Sun H, Dressler G, Wellik D. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biol. 2007;27:7661-8 pubmed
    ..Herein, we demonstrate that Hox11 paralogous proteins form a complex with Pax2 and Eya1 to directly activate expression of Six2 and Gdnf in the metanephric mesenchyme...
  8. Zou D, Erickson C, Kim E, Jin D, Fritzsch B, Xu P. Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear. Hum Mol Genet. 2008;17:3340-56 pubmed publisher
    Haploinsufficiency of the transcription co-activator EYA1 causes branchio-oto-renal syndrome, congenital birth defects that account for as many as 2% of profoundly deaf children; however, the underlying cause for its dosage requirement ..
  9. Nishinakamura R, Matsumoto Y, Nakao K, Nakamura K, Sato A, Copeland N, et al. Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development. 2001;128:3105-15 pubmed
    ..Sall1 is therefore essential for ureteric bud invasion, the initial key step for metanephros development. ..

More Information


  1. Zou D, Silvius D, Fritzsch B, Xu P. Eya1 and Six1 are essential for early steps of sensory neurogenesis in mammalian cranial placodes. Development. 2004;131:5561-72 pubmed
    b>Eya1 encodes a transcriptional co-activator and is expressed in cranial sensory placodes. It interacts with and functions upstream of the homeobox gene Six1 during otic placodal development...
  2. 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
    b>Eya1 is a critical gene for mammalian organogenesis...
  3. Burton Q, Cole L, Mulheisen M, Chang W, Wu D. The role of Pax2 in mouse inner ear development. Dev Biol. 2004;272:161-75 pubmed
  4. Grote D, Souabni A, Busslinger M, Bouchard M. Pax 2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development. 2006;133:53-61 pubmed
    ..Together, these results define Gata3 as a key regulator of nephric duct morphogenesis and guidance in the pro/mesonephric kidney. ..
  5. Xu P, Zheng W, Huang L, Maire P, Laclef C, Silvius D. Six1 is required for the early organogenesis of mammalian kidney. Development. 2003;130:3085-94 pubmed
    ..5, indicating that Six1 is required for the expression of these genes in the metanephric mesenchyme. In contrast, Eya1 expression was unaffected in Six1(-/-) metanephric mesenchyme at E10...
  6. Li X, Oghi K, Zhang J, Krones A, Bush K, Glass C, et al. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 2003;426:247-54 pubmed
  7. Ahmed M, Xu J, Xu P. EYA1 and SIX1 drive the neuronal developmental program in cooperation with the SWI/SNF chromatin-remodeling complex and SOX2 in the mammalian inner ear. Development. 2012;139:1965-77 pubmed publisher
    ..Here, using loss- and gain-of-function models, we show that EYA1 and SIX1 are crucial otic neuronal determination factors upstream of NEUROG1 and NEUROD1...
  8. Purcell P, Oliver G, Mardon G, Donner A, Maas R. Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction. Gene Expr Patterns. 2005;6:110-8 pubmed
    ..b>Eya1 and Dach1 are mammalian homologs of eya and dac, respectively, and although neither Eya1 nor Dach1 knockout mice ..
  9. Mugford J, Sipila P, Kobayashi A, Behringer R, McMahon A. Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo. Dev Biol. 2008;319:396-405 pubmed publisher
    ..This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation. ..
  10. 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
  11. Self M, Lagutin O, Bowling B, Hendrix J, Cai Y, Dressler G, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214-28 pubmed
    ..We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud...
  12. Wellik D, Hawkes P, Capecchi M. Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev. 2002;16:1423-32 pubmed
    ..b>Eya1 expression is also intact...
  13. Sun J, Karoulia Z, Wong E, Ahmed M, Itoh K, Xu P. The phosphatase-transcription activator EYA1 is targeted by anaphase-promoting complex/Cdh1 for degradation at M-to-G1 transition. Mol Cell Biol. 2013;33:927-36 pubmed publisher
    ..Loss-of-function studies have shown that EYA1 is required for cell proliferation and survival during mammalian organogenesis...
  14. Karner C, Das A, Ma Z, Self M, Chen C, Lum L, et al. Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development. Development. 2011;138:1247-57 pubmed publisher
    ..These findings provide novel insights into the molecular mechanisms that regulate progenitor cell differentiation during normal and pathological conditions. ..
  15. Linton J, Martin G, Reichardt L. The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression. Development. 2007;134:2501-9 pubmed
    ..Our results thus place nephronectin and alpha8beta1 integrin in a pathway that regulates Gdnf expression and is essential for kidney development. ..
  16. Bouchard M, de Caprona D, Busslinger M, Xu P, Fritzsch B. Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation. BMC Dev Biol. 2010;10:89 pubmed publisher
    ..All three Pax genes can signal redundantly in the ear with their function being determined primarily by the spatio-temporal expression driven by the three distinct promoters of these genes. ..
  17. Landgraf K, Bollig F, Trowe M, Besenbeck B, Ebert C, Kruspe D, et al. Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in craniofacial development. Mol Cell Biol. 2010;30:5764-75 pubmed publisher
    The eyes absent 1 protein (Eya1) plays an essential role in the development of various organs in both invertebrates and vertebrates...
  18. Ahmed M, Wong E, Sun J, Xu J, Wang F, Xu P. Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating Atoh1 expression in cooperation with Sox2. Dev Cell. 2012;22:377-90 pubmed publisher
    Inner-ear hair cell differentiation requires Atoh1 function, while Eya1, Six1, and Sox2 are coexpressed in sensory progenitors and mutations in these genes cause sensorineural hearing loss...
  19. Carroll T, Park J, Hayashi S, Majumdar A, McMahon A. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell. 2005;9:283-92 pubmed
    ..Together these findings suggest that Wnt9b is a common organizing signal regulating diverse components of the mammalian urogenital system...
  20. Esquela A, Lee S. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol. 2003;257:356-70 pubmed
    ..Our studies suggest that Gdf11 may be important in directing the initial outgrowth of the ureteric bud from the Wolffian duct by controlling the expression of Gdnf in the metanephric mesenchyme. ..
  21. Hulander M, Kiernan A, Blomqvist S, Carlsson P, Samuelsson E, Johansson B, et al. Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice. Development. 2003;130:2013-25 pubmed
    ..Thus, mutations in FOXI1 could prove to cause a Pendred syndrome-like human deafness...
  22. Guo C, Sun Y, Zhou B, Adam R, Li X, Pu W, et al. A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest. 2011;121:1585-95 pubmed publisher
    ..Here, we have identified a genetic pathway involving the Six1/Eya1 transcription complex that regulates cardiovascular and craniofacial development...
  23. Xu P, Adams J, Peters H, Brown M, Heaney S, Maas R. Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet. 1999;23:113-7 pubmed
    Haploinsufficiency for human EYA1, a homologue of the Drosophila melanogaster gene eyes absent (eya), results in the dominantly inherited disorders branchio-oto-renal (BOR) syndrome and branchio-oto (BO) syndrome, which are characterized ..
  24. Zhang H, Wang L, Wong E, Tsang S, Xu P, Lendahl U, et al. An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis. elife. 2017;6: pubmed publisher
    ..b>Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches...
  25. Pitera J, Scambler P, Woolf A. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. Hum Mol Genet. 2008;17:3953-64 pubmed publisher
    ..Fras1 deficiency causes defective interactions between the bud and mesenchyme, correlating with disturbed expression of key nephrogenic molecules. Furthermore, Fras1 may also be required for the formation of normal glomeruli. ..
  26. Hurd E, Poucher H, Cheng K, Raphael Y, Martin D. The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear. Development. 2010;137:3139-50 pubmed publisher
    ..These data indicate that epigenetic regulation of gene expression by CHD7 must be tightly coordinated for proper development of inner ear neuroblasts. ..
  27. Duncan J, Fritzsch B. Continued expression of GATA3 is necessary for cochlear neurosensory development. PLoS ONE. 2013;8:e62046 pubmed publisher
    ..In addition, while Sox2 levels were lower in the Foxg1(Cre):Gata3(f/f) cochlea, Eya1 levels remained normal...
  28. Nie X, Xu J, El Hashash A, Xu P. Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis. Dev Biol. 2011;352:141-51 pubmed publisher
    ..This study uncovers an essential function for Six1 in the MM as an upstream regulator of Grem1 in initiating branching morphogenesis. ..
  29. Ozaki H, Nakamura K, Funahashi J, Ikeda K, Yamada G, Tokano H, et al. Six1 controls patterning of the mouse otic vesicle. Development. 2004;131:551-62 pubmed
    ..In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent. ..
  30. Zou D, Silvius D, Davenport J, Grifone R, Maire P, Xu P. Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Dev Biol. 2006;293:499-512 pubmed
    ..Our data clearly show that Eya1 and Six1 expression in the pouches does not require Pax1/Pax9 function, suggesting that they may function ..
  31. Alkuraya F, Saadi I, Lund J, Turbe Doan A, Morton C, Maas R. SUMO1 haploinsufficiency leads to cleft lip and palate. Science. 2006;313:1751 pubmed
    ..Thus, sumoylation defines a network of genes important for palatogenesis. ..
  32. Tavares A, Cox T, Maxson R, Ford H, Clouthier D. Negative regulation of endothelin signaling by SIX1 is required for proper maxillary development. Development. 2017;144:2021-2031 pubmed publisher
    ..Together, our results illustrate that SIX1 is the central mediator of dorsal mandibular arch identity, thus ensuring separation of bone development between the upper and lower jaws. ..
  33. Eisner A, Pazyra Murphy M, Durresi E, Zhou P, Zhao X, Chadwick E, et al. The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis. Dev Cell. 2015;33:22-35 pubmed publisher
    ..Here, we conducted a small hairpin RNA (shRNA) screen of the phosphatome and identified Eya1 as a positive regulator of Shh signaling...
  34. 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...
  35. Kalatzis V, Sahly I, El Amraoui A, Petit C. Eya1 expression in the developing ear and kidney: towards the understanding of the pathogenesis of Branchio-Oto-Renal (BOR) syndrome. Dev Dyn. 1998;213:486-99 pubmed
    ..The gene underlying this syndrome, EYA1, is homologous to the Drosophila developmental gene eyes absent which encodes a transcriptional co-activator ..
  36. Caubit X, Thangarajah R, Theil T, Wirth J, Nothwang H, Ruther U, et al. Mouse Dac, a novel nuclear factor with homology to Drosophila dachshund shows a dynamic expression in the neural crest, the eye, the neocortex, and the limb bud. Dev Dyn. 1999;214:66-80 pubmed
    ..FISH analysis reveals that human DAC maps to chromosome 13q22.3-23 and further fine-mapping defined a position of the DAC gene at 54cM or 13q21.1, a locus that associates with mental retardation and skeletal abnormalities. ..
  37. Clark S, Fee B, Cleveland J. Misexpression of the eyes absent family triggers the apoptotic program. J Biol Chem. 2002;277:3560-7 pubmed
    ..fmk, suggesting that mitochondria are a major target in Eya-induced apoptosis. These results support the concept that inappropriate changes in the steady state levels of Eya proteins may trigger programmed cell deaths during development. ..
  38. Fairbridge N, Dawe C, Niri F, Kooistra M, King Jones K, McDermid H. Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors. Birth Defects Res A Clin Mol Teratol. 2010;88:619-25 pubmed publisher
    ..1Hemc) mutant heads confirmed downregulation of transcription factors Alx1/Cart1, Dlx5, Eya1, and Six1...
  39. Walker K, Sims Lucas S, Caruana G, Cullen McEwen L, Li J, Sarraj M, et al. Betaglycan is required for the establishment of nephron endowment in the mouse. PLoS ONE. 2011;6:e18723 pubmed publisher
    ..in the gene regulatory network that governs metanephric development, including significant increases in Pax2, Eya1, Gdnf, Ret, Wnt4, and Wt1 expression. Conversely, gene expression in null kidneys was normal until e13...
  40. Boivin F, Sarin S, Lim J, Javidan A, Svajger B, Khalili H, et al. Stromally expressed β-catenin modulates Wnt9b signaling in the ureteric epithelium. PLoS ONE. 2015;10:e0120347 pubmed publisher
    ..We propose that β-catenin in the renal stroma modulates a genetic program in ureteric epithelium that is required for the induction of nephron progenitors. ..
  41. Minoux M, Kratochwil C, Ducret S, Amin S, Kitazawa T, Kurihara H, et al. Mouse Hoxa2 mutations provide a model for microtia and auricle duplication. Development. 2013;140:4386-97 pubmed publisher
    ..Hoxa2 partly controls the morphogenesis of the pinna through the BMP signalling pathway and expression of Eya1, which in humans is involved in branchio-oto-renal syndrome...
  42. Grifone R, Demignon J, Giordani J, Niro C, Souil E, Bertin F, et al. Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo. Dev Biol. 2007;302:602-16 pubmed
    In mammals, Pax3, Six4, Six1 and Six5 genes are co-expressed with Eya1, Eya2 and Eya4 genes during mouse somitogenesis...
  43. Grifone R, Laclef C, Spitz F, Lopez S, Demignon J, Guidotti J, et al. Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype. Mol Cell Biol. 2004;24:6253-67 pubmed
    ..We also show that among the Six and Eya gene products expressed in mouse skeletal muscle, Six1 and Eya1 proteins accumulate preferentially in the nuclei of fast-twitch muscles...
  44. Zhang Y, Knosp B, Maconochie M, Friedman R, Smith R. A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10. J Assoc Res Otolaryngol. 2004;5:295-304 pubmed
    Allele variants of EYA1 and EYA4, two members of the vertebrate Eya gene family, underlie two types of inherited human deafness, branchio-oto-renal (BOR) syndrome and DFNA10, respectively...
  45. Lu K, Reddy R, Berika M, Warburton D, El Hashash A. Abrogation of Eya1/Six1 disrupts the saccular phase of lung morphogenesis and causes remodeling. Dev Biol. 2013;382:110-23 pubmed publisher
    The Eya1 gene encodes a transcriptional co-activator that acts with Six1 to control the development of different organs...
  46. Huang T, Krimm R. BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol. 2014;386:308-20 pubmed publisher
    ..Spatial and temporal differences in BDNF and NT4 expression can regulate differential gene expression in vivo and determine their specific roles during development. ..
  47. Musharraf A, Kruspe D, Tomasch J, Besenbeck B, Englert C, Landgraf K. BOR-syndrome-associated Eya1 mutations lead to enhanced proteasomal degradation of Eya1 protein. PLoS ONE. 2014;9:e87407 pubmed publisher
    Mutations in the human EYA1 gene have been associated with several human diseases including branchio-oto (BO) and branchio-oto-renal (BOR) syndrome, as well as congenital cataracts and ocular anterior segment anomalies...
  48. Ring B, Cordes S, Overbeek P, Barsh G. Regulation of mouse lens fiber cell development and differentiation by the Maf gene. Development. 2000;127:307-17 pubmed
    ..for gene targeting of Prox1 and Sox1; however, expression of these genes is grossly normal, as is expression of Eya1, Eya2, Pax6, and Sox2...
  49. Borsani G, DeGrandi A, Ballabio A, Bulfone A, Bernard L, Banfi S, et al. EYA4, a novel vertebrate gene related to Drosophila eyes absent. Hum Mol Genet. 1999;8:11-23 pubmed
    ..On the basis of map position and expression pattern, EYA4 is a candidate for oculo-dento-digital (ODD) syndrome, but no EYA4 mutations were found in a panel of ODD patients. ..
  50. Ohto H, Kamada S, Tago K, Tominaga S, Ozaki H, Sato S, et al. Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya. Mol Cell Biol. 1999;19:6815-24 pubmed
    ..Coexpression of Six2, Six4, or Six5 induced nuclear translocation of Eya1, Eya2, and Eya3, which were otherwise distributed in the cytoplasm...
  51. Kuure S, Sainio K, Vuolteenaho R, Ilves M, Wartiovaara K, Immonen T, et al. Crosstalk between Jagged1 and GDNF/Ret/GFRalpha1 signalling regulates ureteric budding and branching. Mech Dev. 2005;122:765-80 pubmed
    ..Thus, the data provide evidence for a novel crosstalk between Notch and Ret/GFRalpha1 signalling during early nephrogenesis. ..
  52. Goudreau G, Petrou P, Reneker L, Graw J, Löster J, Gruss P. Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6 haploinsufficient lens phenotype. Proc Natl Acad Sci U S A. 2002;99:8719-24 pubmed
    ..Our findings thus provide a mechanism implicating gene regulatory interactions between Pax6 and Six3 in the tissue-specific defects found in Pax6 heterozygous mice. ..
  53. Poladia D, Kish K, Kutay B, Hains D, Kegg H, Zhao H, et al. Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol. 2006;291:325-39 pubmed
    ..By in situ hybridization, regions of mutant mesenchyme near the ureteric bud(s) express Eya1 and Six1, but not Six2, Sall1, or Pax2, while the ureteric bud expresses Ret and Pax2 normally...
  54. Xu J, Xu P. Eya-six are necessary for survival of nephrogenic cord progenitors and inducing nephric duct development before ureteric bud formation. Dev Dyn. 2015;244:866-73 pubmed publisher
    ..5-E11.0, similar to that observed in Eya1(-/-) embryos...
  55. Niu H, Makmura L, Shen T, Sheth S, Blair K, Friedman R. Identification of two major loci that suppress hearing loss and cochlear dysmorphogenesis in Eya1bor/bor mice. Genomics. 2006;88:302-8 pubmed
    The Eya1(bor) mutant hypomorph contains an intracisternal A particle insertion in intron 7 of the Eya1 gene that results in a 50% reduction in wild-type mRNA levels...
  56. Daou N, Lecolle S, Lefebvre S, Della Gaspera B, Charbonnier F, Chanoine C, et al. A new role for the calcineurin/NFAT pathway in neonatal myosin heavy chain expression via the NFATc2/MyoD complex during mouse myogenesis. Development. 2013;140:4914-25 pubmed publisher
    ..Altogether, our findings demonstrate that the calcineurin/NFAT pathway plays a new role in establishing the early muscle fiber type in immature myofibers during embryogenesis. ..
  57. Xu J, Ueno H, Xu C, Chen B, Weissman I, Xu P. Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti. Nat Commun. 2017;8:15046 pubmed publisher
    ..These multipotent progenitors originate from Eya1-expressing otic progenitors...
  58. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, et al. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet. 1997;15:157-64 pubmed
    ..This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 ..
  59. Wang C, Gargollo P, Guo C, Tang T, Mingin G, Sun Y, et al. Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development. Dev Biol. 2011;360:186-94 pubmed publisher
    The evolutionarily conserved Six1-Eya1 transcription complex is central to mammalian organogenesis, and deletion of these genes in mice results in developmental anomalies of multiple organs that recapitulate human branchio-oto-renal (BOR) ..
  60. Rumballe B, Georgas K, Combes A, Ju A, Gilbert T, Little M. Nephron formation adopts a novel spatial topology at cessation of nephrogenesis. Dev Biol. 2011;360:110-22 pubmed publisher
    ..We propose that this phase of nephron formation represents an acceleration of differentiation within the cap mesenchyme due to a displacement of signals within the nephrogenic niche. ..
  61. James R, Kamei C, Wang Q, Jiang R, Schultheiss T. Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells. Development. 2006;133:2995-3004 pubmed
    ..mesenchyme, and do not express several other factors required for metanephric kidney formation, including Eya1, Six2, Pax2, Sall1 and Gdnf...
  62. Grieshammer U, Le Ma -, Plump A, Wang F, Tessier Lavigne M, Martin G. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell. 2004;6:709-17 pubmed
    ..Thus our data identify an intercellular signaling system that restricts, directly or indirectly, the extent of the Gdnf expression domain, thereby precisely positioning the site of kidney induction. ..
  63. Ruf R, Xu P, Silvius D, Otto E, Beekmann F, Muerb U, et al. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci U S A. 2004;101:8090-5 pubmed
    ..Haploinsufficiency for the human gene EYA1, a homologue of the Drosophila gene eyes absent (eya), causes BOR and BO syndromes...
  64. Yallowitz A, Hrycaj S, Short K, Smyth I, Wellik D. Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma. PLoS ONE. 2011;6:e23410 pubmed publisher
  65. Ozaki H, Watanabe Y, Ikeda K, Kawakami K. Impaired interactions between mouse Eyal harboring mutations found in patients with branchio-oto-renal syndrome and Six, Dach, and G proteins. J Hum Genet. 2002;47:107-16 pubmed
    Mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome as well as for other ocular defects...
  66. Sun Y, Li X. The canonical wnt signal restricts the glycogen synthase kinase 3/fbw7-dependent ubiquitination and degradation of eya1 phosphatase. Mol Cell Biol. 2014;34:2409-17 pubmed publisher
    Haploinsufficiency of Eya1 causes the branchio-oto-renal (BOR) syndrome, and abnormally high levels of Eya1 are linked to breast cancer progression and poor prognosis...
  67. Gerber S, Steinberg F, Beyeler M, Villiger P, Trueb B. The murine Fgfrl1 receptor is essential for the development of the metanephric kidney. Dev Biol. 2009;335:106-19 pubmed publisher
    ..We also observed a loss of Pax2 positive nephron precursor cells and an increase of apoptosis in the cortical zone of the remnant kidney. Fgfrl1 is therefore essential for mesenchymal differentiation in the early steps of nephrogenesis. ..
  68. Freyer L, Morrow B. Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle. Dev Dyn. 2010;239:1708-22 pubmed publisher
    ..which canonical Wnt signaling sets boundaries for pattern formation in the otic vesicle (OV), we examined Tbx1 and Eya1-Six1 downstream of activated beta-catenin...
  69. Nie X, Sun J, Gordon R, Cai C, Xu P. SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation. Development. 2010;137:755-65 pubmed publisher
    ..embryos by specifically expressing Six1 in the metanephric mesenchyme, but not the ureter, under control of the Eya1 promoter...
  70. Lokmane L, Heliot C, Garcia Villalba P, Fabre M, Cereghini S. vHNF1 functions in distinct regulatory circuits to control ureteric bud branching and early nephrogenesis. Development. 2010;137:347-57 pubmed publisher
  71. Lilleväli K, Matilainen T, Karis A, Salminen M. Partially overlapping expression of Gata2 and Gata3 during inner ear development. Dev Dyn. 2004;231:775-81 pubmed
    ..5 and Gata3 expression was unchanged. In contrast, a delay and strong reduction of Gata2 expression was detected in Gata3-/- otic epithelium...
  72. Xu J, Liu H, Park J, Lan Y, Jiang R. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis. Development. 2014;141:1442-52 pubmed publisher
  73. Ranghini E, Dressler G. Evidence for intermediate mesoderm and kidney progenitor cell specification by Pax2 and PTIP dependent mechanisms. Dev Biol. 2015;399:296-305 pubmed publisher
    ..These data provide evidence that Pax2 specifies the intermediate mesoderm and renal epithelial cells through epigenetic mechanisms and in part by repressing paraxial mesodermal fate. ..