Gene Symbol: Pou4f3
Description: POU domain, class 4, transcription factor 3
Alias: Brn3.1, Brn3c, ddl, dreidel, POU domain, class 4, transcription factor 3, brain-3C, brain-specific homeobox POU domain protein 3C, brn-3C
Species: mouse
Products:     Pou4f3

Top Publications

  1. Keithley E, Erkman L, Bennett T, Lou L, Ryan A. Effects of a hair cell transcription factor, Brn-3.1, gene deletion on homozygous and heterozygous mouse cochleas in adulthood and aging. Hear Res. 1999;134:71-6 pubmed
    ..There appeared to be no effect of Brn-3.1 haploinsufficiency on the mouse cochlea, implying that one intact copy of the gene is sufficient to maintain a normal cochlea. ..
  2. Xiang M, Maklad A, Pirvola U, Fritzsch B. Brn3c null mutant mice show long-term, incomplete retention of some afferent inner ear innervation. BMC Neurosci. 2003;4:2 pubmed
    Ears of Brn3c null mutants develop immature hair cells, identifiable only by certain molecular markers, and undergo apoptosis in neonates...
  3. Gerrero M, McEvilly R, Turner E, Lin C, O Connell S, Jenne K, et al. Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs. Proc Natl Acad Sci U S A. 1993;90:10841-5 pubmed
    ..Brn-3.0, Brn-3.1, and the Drosophila tI-POU share an N-terminal region of homology, referred to as the "POU-IV box," which is similar to a conserved functional domain in the c-myc gene family. ..
  4. Xiang M, Gan L, Li D, Zhou L, Chen Z, Wagner D, et al. Role of the Brn-3 family of POU-domain genes in the development of the auditory/vestibular, somatosensory, and visual systems. Cold Spring Harb Symp Quant Biol. 1997;62:325-36 pubmed
  5. Xiang M. Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion cell precursors. Dev Biol. 1998;197:155-69 pubmed
  6. Badea T, Williams J, Smallwood P, Shi M, Motajo O, Nathans J. Combinatorial expression of Brn3 transcription factors in somatosensory neurons: genetic and morphologic analysis. J Neurosci. 2012;32:995-1007 pubmed publisher
    The three members of the Brn3 family of POU-domain transcription factors (Brn3a/Pou4f1, Brn3b/Pou4f2, and Brn3c/Pou4f3) are expressed in overlapping subsets of visual, auditory/vestibular, and somatosensory neurons...
  7. Xiang M, Gan L, Zhou L, Klein W, Nathans J. Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement, and impaired suckling. Proc Natl Acad Sci U S A. 1996;93:11950-5 pubmed
  8. Badea T, Nathans J. Morphologies of mouse retinal ganglion cells expressing transcription factors Brn3a, Brn3b, and Brn3c: analysis of wild type and mutant cells using genetically-directed sparse labeling. Vision Res. 2011;51:269-79 pubmed publisher
    ..The roles of the closely related family members, Brn3a/Pou4f1 and Brn3c/Pou4f3 in RGC development are less clear...
  9. Xiang M, Zhou L, Macke J, Yoshioka T, Hendry S, Eddy R, et al. The Brn-3 family of POU-domain factors: primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neurons. J Neurosci. 1995;15:4762-85 pubmed
    ..ganglion cells (alpha and beta cells); anti-Brn-3b immunoreactivity was present in all ganglion cells; and anti-Brn3c immunoreactivity was confined to the small ganglion cells...

More Information


  1. Jain V, Ravindran E, Dhingra N. Differential expression of Brn3 transcription factors in intrinsically photosensitive retinal ganglion cells in mouse. J Comp Neurol. 2012;520:742-55 pubmed publisher
    ..The Brn3 family of class IV POU-domain transcription factors (Brn3a, Brn3b, and Brn3c) is involved in the regulation of differentiation, dendritic stratification, and axonal projection of retinal ..
  2. Gan L, Xiang M, Zhou L, Wagner D, Klein W, Nathans J. POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells. Proc Natl Acad Sci U S A. 1996;93:3920-5 pubmed
    ..In Brn-3b (-/-) mice other neurons within the retina and brain are minimally or not at all affected. These experiments indicate that Brn-3b plays an essential role in the development of specific ganglion cell types. ..
  3. Towers E, Kelly J, Sud R, Gale J, Dawson S. Caprin-1 is a target of the deafness gene Pou4f3 and is recruited to stress granules in cochlear hair cells in response to ototoxic damage. J Cell Sci. 2011;124:1145-55 pubmed publisher
    ..b>Pou4f3 is essential for the survival of auditory sensory hair cells and several mutations in human POU4F3 cause hearing ..
  4. Jahan I, Pan N, Kersigo J, Fritzsch B. Neurod1 suppresses hair cell differentiation in ear ganglia and regulates hair cell subtype development in the cochlea. PLoS ONE. 2010;5:e11661 pubmed publisher
    ..Through this and other feedback, Neurod1 suppresses alternate fates of neurons to differentiate as hair cells and regulates hair cell subtypes. ..
  5. Clough R, Sud R, Davis Silberman N, Hertzano R, Avraham K, Holley M, et al. Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity. Biochem Biophys Res Commun. 2004;324:372-81 pubmed
    ..Additionally, BDNF expression is reduced in the inner ear of a Brn-3c mutant mouse during embryogenesis. Our data suggest that Brn-3c may play a role in regulating neurotrophin gene expression in the inner ear. ..
  6. Shi M, Kumar S, Motajo O, Kretschmer F, Mu X, Badea T. Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification. PLoS ONE. 2013;8:e76347 pubmed publisher
    ..and lamination defects in Brn3a positive RGCs, and selectively affects survival and morphology of specific Brn3c (Pou4f3) positive RGC types. Brn3a and Brn3b interact synergistically to control RGC numbers...
  7. Hertzano R, Dror A, Montcouquiol M, Ahmed Z, Ellsworth B, Camper S, et al. Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system. Eur J Neurosci. 2007;25:999-1005 pubmed
    A dominant mutation of the gene encoding the POU4F3 transcription factor underlies human non-syndromic progressive hearing loss DFNA15...
  8. Wang S, Mu X, Bowers W, Kim D, Plas D, Crair M, et al. Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. Development. 2002;129:467-77 pubmed
    ..During retinal ganglion cell differentiation, Brn3b is expressed first, followed by Brn3a and Brn3c. Targeted deletion of Brn3b, but not Brn3a or Brn3c, leads to a loss of most retinal ganglion cells before birth...
  9. Masuda M, Pak K, Chavez E, Ryan A. TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in nonsensory cochlear epithelium by ATOH1. Dev Biol. 2012;372:68-80 pubmed publisher
    ..We previously identified closely-spaced TF binding motifs located 8.2-8.5 kb 5' to the ATG of the murine Pou4f3 gene, a gene required for late hair cell (HC) differentiation and survival...
  10. Erkman L, McEvilly R, Luo L, Ryan A, Hooshmand F, O Connell S, et al. Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development. Nature. 1996;381:603-6 pubmed
    ..Mutation of Brn-3.1 results in complete deafness, owing to a failure of hair cells to appear in the inner ear, with subsequent loss of cochlear and vestibular ganglia. ..
  11. Hertzano R, Montcouquiol M, Rashi Elkeles S, Elkon R, Yücel R, Frankel W, et al. Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum Mol Genet. 2004;13:2143-53 pubmed
    b>Pou4f3 (Brn3.1, Brn3c) is a class IV POU domain transcription factor that has a central function in the development of all hair cells in the human and mouse inner ear sensory epithelia...
  12. Xiang M, Gan L, Li D, Chen Z, Zhou L, O Malley B, et al. Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. Proc Natl Acad Sci U S A. 1997;94:9445-50 pubmed
  13. Xiang M, Gao W, Hasson T, Shin J. Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells. Development. 1998;125:3935-46 pubmed
    ..These data indicate a crucial role for Brn-3c in maturation, survival and migration of hair cells, but not in proliferation or commitment of hair cell progenitors. ..
  14. McEvilly R, Erkman L, Luo L, Sawchenko P, Ryan A, Rosenfeld M. Requirement for Brn-3.0 in differentiation and survival of sensory and motor neurons. Nature. 1996;384:574-7 pubmed
    ..Deletion of Brn-3.0 also alters either differentiation, migration or survival of specific central neuronal populations. ..
  15. Kiernan A, Pelling A, Leung K, Tang A, Bell D, Tease C, et al. Sox2 is required for sensory organ development in the mammalian inner ear. Nature. 2005;434:1031-5 pubmed
  16. Wang T, Chai R, Kim G, Pham N, Jansson L, Nguyen D, et al. Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Nat Commun. 2015;6:6613 pubmed publisher
    ..Lastly, stabilized ß-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration. ..
  17. Mahrt E, Perkel D, Tong L, Rubel E, Portfors C. Engineered deafness reveals that mouse courtship vocalizations do not require auditory experience. J Neurosci. 2013;33:5573-83 pubmed publisher
    ..We conclude that mouse courtship vocalizations are not acquired through auditory feedback-dependent learning...
  18. Li R, Wu F, Ruonala R, Sapkota D, Hu Z, Mu X. Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells. PLoS ONE. 2014;9:e92105 pubmed publisher
  19. Cox B, Chai R, Lenoir A, Liu Z, Zhang L, Nguyen D, et al. Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development. 2014;141:816-29 pubmed publisher
    ..Here, we developed two genetic strategies to ablate neonatal mouse cochlear hair cells in vivo. Both Pou4f3(DTR/+) and Atoh1-CreER™; ROSA26(DTA/+) alleles allowed selective and inducible hair cell ablation...
  20. Moraes F, Novoa A, Jerome Majewska L, Papaioannou V, Mallo M. Tbx1 is required for proper neural crest migration and to stabilize spatial patterns during middle and inner ear development. Mech Dev. 2005;122:199-212 pubmed
    ..The inability of the Tbx1(-/-) embryos to keep properly segregated functional domains in the otocyst is likely the cause of the strong inner ear phenotypes observed in these mutants. ..
  21. Tong L, Strong M, Kaur T, Juiz J, Oesterle E, HUME C, et al. Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons. J Neurosci. 2015;35:7878-91 pubmed publisher
    ..Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter...
  22. Frenz S, Rak K, Völker J, Jürgens L, Scherzad A, Schendzielorz P, et al. Mosaic pattern of Cre recombinase expression in cochlear outer hair cells of the Brn3.1 Cre mouse. Neuroreport. 2015;26:309-13 pubmed publisher
    ..Also, the unchanged hearing capacity and structural integrity of the organ of Corti in available reporter lines indicate that they may be useful tools for hearing research. ..
  23. Kaur T, Hirose K, Rubel E, Warchol M. Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle. Front Cell Neurosci. 2015;9:150 pubmed publisher
    ..mice in which the gene for the human diphtheria toxin receptor (huDTR) was inserted under regulation of the Pou4f3 promoter. Hair cells in such mice can be selectively lesioned by systemic treatment with diphtheria toxin (DT)...
  24. Tornari C, Towers E, Gale J, Dawson S. Regulation of the orphan nuclear receptor Nr2f2 by the DFNA15 deafness gene Pou4f3. PLoS ONE. 2014;9:e112247 pubmed publisher
    Hair cells are the mechanotransducing cells of the inner ear that are essential for hearing and balance. POU4F3--a POU-domain transcription factor selectively expressed by these cells--has been shown to be essential for hair cell ..
  25. Brzezinski J, Kim E, Johnson J, Reh T. Ascl1 expression defines a subpopulation of lineage-restricted progenitors in the mammalian retina. Development. 2011;138:3519-31 pubmed publisher
    ..Our results link progenitor heterogeneity to different fate outcomes. We show that Ascl1 expression defines a competence-restricted progenitor lineage in the retina, providing a new mechanism to explain fate diversification. ..
  26. Masuda M, Dulon D, Pak K, Mullen L, Li Y, Erkman L, et al. Regulation of POU4F3 gene expression in hair cells by 5' DNA in mice. Neuroscience. 2011;197:48-64 pubmed publisher
    The POU-domain transcription POU4F3 is expressed in the sensory cells of the inner ear. Expression begins shortly after commitment to the hair cell (HC) fate, and continues throughout life...
  27. Theil T, McLean Hunter S, Zörnig M, Moroy T. Mouse Brn-3 family of POU transcription factors: a new aminoterminal domain is crucial for the oncogenic activity of Brn-3a. Nucleic Acids Res. 1993;21:5921-9 pubmed
    ..In addition, our data indicate that Brn-3b acts as an inhibitor of Brn-3a(l) activity. ..
  28. Salminen M, Meyer B, Bober E, Gruss P. Netrin 1 is required for semicircular canal formation in the mouse inner ear. Development. 2000;127:13-22 pubmed
  29. Sud R, Jones C, Banfi S, Dawson S. Transcriptional regulation by Barhl1 and Brn-3c in organ-of-Corti-derived cell lines. Brain Res Mol Brain Res. 2005;141:174-80 pubmed
    ..In addition, we analyzed the effect of Barhl1 on the promoters of the neurotrophin genes NT-3 and BDNF in OC-1 and OC-2 cell lines. However, Barhl1 was not found to directly regulate neurotrophin promoter constructs in these cells. ..
  30. Wagner K, Wagner N, Vidal V, Schley G, Wilhelm D, Schedl A, et al. The Wilms' tumor gene Wt1 is required for normal development of the retina. EMBO J. 2002;21:1398-405 pubmed
    ..Taken together, our findings demonstrate a continuous requirement for Wt1 in normal retina formation with a critical role in Pou4f2-dependent ganglion cell differentiation. ..
  31. Bucks S, Cox B, Vlosich B, Manning J, Nguyen T, Stone J. Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice. elife. 2017;6: pubmed publisher
    ..These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury. ..
  32. Keats B, Berlin C. Genomics and hearing impairment. Genome Res. 1999;9:7-16 pubmed
    ..The genes that have been identified encode diaphanous (HDIA1), alpha-tectorin (TECTA), the transcription factor POU4F3, connexin 26 (GJB2), and two unconventional myosins (MYO7A and MYO15), and four novel proteins (PDS, COCH, DFNA5, ..
  33. Zou M, Li S, Klein W, Xiang M. Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Dev Biol. 2012;364:114-27 pubmed publisher
    ..Our results together demonstrate a critical role for Brn3a in generating DRG sensory neuron diversity and regulating sensory afferent projections to the central targets. ..
  34. Wallis D, Hamblen M, Zhou Y, Venken K, Schumacher A, Grimes H, et al. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development. 2003;130:221-32 pubmed
    ..Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death. ..
  35. Klingenspor M, Bodnar J, Welch C, Xia Y, Lusis A, Reue K. Localization of ubiquitin gene family members to mouse chromosomes 5, 11, and 18. Mamm Genome. 1997;8:789-90 pubmed
  36. Weston M, Pierce M, Jensen Smith H, Fritzsch B, Rocha Sanchez S, Beisel K, et al. MicroRNA-183 family expression in hair cell development and requirement of microRNAs for hair cell maintenance and survival. Dev Dyn. 2011;240:808-19 pubmed publisher
    ..Results suggest that hair cell miRNAs subdue cochlear gradient gene expression and are required for hair cell maintenance and survival. ..
  37. Fukui H, Wong H, Beyer L, Case B, Swiderski D, Di Polo A, et al. BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice. Sci Rep. 2012;2:838 pubmed publisher
    ..A mouse with Pou4f3 loss of function has no hair cells and a subsequent, progressive degeneration of auditory neurons...
  38. Kopecky B, Jahan I, Fritzsch B. Correct timing of proliferation and differentiation is necessary for normal inner ear development and auditory hair cell viability. Dev Dyn. 2013;242:132-47 pubmed publisher
    ..be due to mis-regulation of genes necessary for neurosensory formation and maintenance, such as Neurod1, Atoh1, Pou4f3, and Barhl1...
  39. Deng M, Pan L, Xie X, Gan L. Differential expression of LIM domain-only (LMO) genes in the developing mouse inner ear. Gene Expr Patterns. 2006;6:857-63 pubmed
    ..Thus, the regionalized expression patterns of LMO1-4 are closely associated with the morphogenesis of the inner ear. ..
  40. Walters B, Coak E, Dearman J, Bailey G, Yamashita T, Kuo B, et al. In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice. Cell Rep. 2017;19:307-320 pubmed publisher
    ..Co-activation of GATA3 or POU4F3 and ATOH1 promoted conversion of SCs to HCs in adult mice...
  41. Yang H, Gan J, Xie X, Deng M, Feng L, Chen X, et al. Gfi1-Cre knock-in mouse line: A tool for inner ear hair cell-specific gene deletion. Genesis. 2010;48:400-6 pubmed publisher
    ..Throughout inner ear development, lacZ expression was detected only in hair cells. Thus, Gfi1-Cre knock-in mouse line provides a useful tool for gene manipulations specifically in inner ear hair cells. ..
  42. Atar O, Avraham K. Anti-apoptotic factor z-Val-Ala-Asp-fluoromethylketone promotes the survival of cochlear hair cells in a mouse model for human deafness. Neuroscience. 2010;168:851-7 pubmed publisher
    ..Our research focused on protecting hair cells from cell death occurring in a genetic model for human deafness. POU4F3 is a transcription factor associated with human hearing impairment...
  43. Taranda J, Ballestero J, Hiel H, de Souza F, Wedemeyer C, Gómez Casati M, et al. Constitutive expression of the alpha10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing. J Assoc Res Otolaryngol. 2009;10:397-406 pubmed publisher
    ..whose IHCs constitutively express alpha10 into adulthood by expressing the alpha10 cDNA under the control of the Pou4f3 gene promoter...
  44. Marcucci F, Murcia Belmonte V, Wang Q, Coca Y, Ferreiro Galve S, Kuwajima T, et al. The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells. Cell Rep. 2016;17:3153-3164 pubmed publisher
    ..Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. ..
  45. Morsli H, Choo D, Ryan A, Johnson R, Wu D. Development of the mouse inner ear and origin of its sensory organs. J Neurosci. 1998;18:3327-35 pubmed
    ..Based on the gene expression patterns, the anterior and lateral cristae may share a common origin. Similarly, three sensory organs, the macula utriculi, macula sacculi, and cochlea, seem to arise from a single region of the otocyst. ..
  46. Golub J, Tong L, Ngyuen T, Hume C, Palmiter R, Rubel E, et al. Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin. J Neurosci. 2012;32:15093-105 pubmed publisher
    ..of hair cells in the adult mouse utricle by inserting the human diphtheria toxin receptor (DTR) gene into the Pou4f3 gene, which encodes a hair cell-specific transcription factor...
  47. Scheffer D, Shen J, Corey D, Chen Z. Gene Expression by Mouse Inner Ear Hair Cells during Development. J Neurosci. 2015;35:6366-80 pubmed publisher
    ..We found that many of the known hereditary deafness genes are much more highly expressed in hair cells than surrounding cells, suggesting that genes preferentially expressed in hair cells are good candidates for unknown deafness genes. ..
  48. Kurioka T, Lee M, Heeringa A, Beyer L, Swiderski D, Kanicki A, et al. Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus. Neuroscience. 2016;332:242-57 pubmed publisher
    ..Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination. ..
  49. Costa A, Powell L, Lowell S, Jarman A. Atoh1 in sensory hair cell development: constraints and cofactors. Semin Cell Dev Biol. 2017;65:60-68 pubmed publisher
    ..We particularly focus on the possible roles of Gfi1 and Pou4f3, drawing from studies in mouse, Drosophila and C. elegans.
  50. Hu X, Huang J, Feng L, Fukudome S, Hamajima Y, Lin J. Sonic hedgehog (SHH) promotes the differentiation of mouse cochlear neural progenitors via the Math1-Brn3.1 signaling pathway in vitro. J Neurosci Res. 2010;88:927-35 pubmed publisher
    ..Taken together, our data suggest that SHH plays an important role in the promotion of auditory hair cell differentiation via the Math1-Brn3.1 signaling pathway. ..
  51. Morsli H, Tuorto F, Choo D, Postiglione M, Simeone A, Wu D. Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. Development. 1999;126:2335-43 pubmed
    ..These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs...
  52. Theil T, Zechner U, Klett C, Adolph S, Moroy T. Chromosomal localization and sequences of the murine Brn-3 family of developmental control genes. Cytogenet Cell Genet. 1994;66:267-71 pubmed
    ..Fluorescence in situ hybridization experiments with mouse chromosomes showed that Brn-3a maps to mouse chromosome 14E1-3, Brn-3b to XF1-5 and Brn-3c to 18B3-E1. ..
  53. Probst F, Camper S. The role of mouse mutants in the identification of human hereditary hearing loss genes. Hear Res. 1999;130:1-6 pubmed
    ..In recent years, the identification of five different mutated genes in the mouse (Pax3, Mitf; Myo7a, Pou4f3, and Myo15) has led directly to the identification of mutations in families with either congenital sensorineural ..