Genomes and Genes
Gene Symbol: Pou3f4
Description: POU domain, class 3, transcription factor 4
Alias: Brn-4, Brn4, OTF-9, Otf9, Slf, oct-9, POU domain, class 3, transcription factor 4, brain-4 class III POU-domain protein, brain-specific homeobox/POU domain protein 4, octamer-binding protein 9, octamer-binding transcription factor 9, sex linked fidget
- CHAO C, Loomis Z, Lee J, Sussel L. Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Dev Biol. 2007;312:523-32 pubmed..Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells. ..
- Song M, Choi S, Wu L, Oh S, Lee H, Lee D, et al. Pou3f4 deficiency causes defects in otic fibrocytes and stria vascularis by different mechanisms. Biochem Biophys Res Commun. 2011;404:528-33 pubmed publisherDFN3, the most prevalent X-linked hearing loss, is caused by mutations in the POU3F4 gene...
- Phippard D, Lu L, Lee D, Saunders J, Crenshaw E. Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear. J Neurosci. 1999;19:5980-9 pubmedTargeted mutagenesis in mice demonstrates that the POU-domain gene Brn4/Pou3f4 plays a crucial role in the patterning of the mesenchymal compartment of the inner ear...
- Heller R, Stoffers D, Liu A, Schedl A, Crenshaw E, Madsen O, et al. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. Dev Biol. 2004;268:123-34 pubmedBrain 4 (Brn4/Pou3f4) and Pax6 are POU-homeodomain and paired-homeodomain transcription factors, respectively, that are expressed in the brain and the glucagon-expressing cells in the pancreas...
- Robert Moreno l, Naranjo S, de la Calle Mustienes E, G mez Skarmeta J, Alsina B. Characterization of new otic enhancers of the pou3f4 gene reveal distinct signaling pathway regulation and spatio-temporal patterns. PLoS ONE. 2010;5:e15907 pubmed publisherb>POU3F4 is a member of the POU-homedomain transcription factor family with a prominent role in inner ear development...
- Sussel L, Kalamaras J, Hartigan O Connor D, Meneses J, Pedersen R, Rubenstein J, et al. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development. 1998;125:2213-21 pubmed..1. We propose that Nkx2.2 is required for the final differentiation of pancreatic beta cells, and in its absence, beta cells are trapped in an incompletely differentiated state. ..
- Xia A, Kikuchi T, Minowa O, Katori Y, Oshima T, Noda T, et al. Late-onset hearing loss in a mouse model of DFN3 non-syndromic deafness: morphologic and immunohistochemical analyses. Hear Res. 2002;166:150-8 pubmed
- Artner I, Blanchi B, Raum J, Guo M, Kaneko T, Cordes S, et al. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007;104:3853-8 pubmed..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells. ..
- Schwitzgebel V, Scheel D, Conners J, Kalamaras J, Lee J, Anderson D, et al. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development. 2000;127:3533-42 pubmed..5. Although not detected in cells expressing islet hormones or the islet transcription factors Isl1, Brn4, Pax6 or PDX1, neurogenin3 is detected along with early islet differentiation factors Nkx6.1 and Nkx2...
- Anderson S, Qiu M, Bulfone A, Eisenstat D, Meneses J, Pedersen R, et al. Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron. 1997;19:27-37 pubmed..Several lines of evidence suggest that mutations in Dlx-1 and Dlx-2 produce abnormalities in the development of the striatal subventricular zone and in the differentiation of striatal matrix neurons. ..
- Sobol S, Teng X, Crenshaw E. Abnormal mesenchymal differentiation in the superior semicircular canal of brn4/pou3f4 knockout mice. Arch Otolaryngol Head Neck Surg. 2005;131:41-5 pubmed..Mutations in the Brn4/Pou3f4 gene result in characteristic inner ear abnormalities in mutant mouse pedigrees, and the findings in these mice ..
- Chervenak A, Hakim I, Barald K. Spatiotemporal expression of Zic genes during vertebrate inner ear development. Dev Dyn. 2013;242:897-908 pubmed publisher..Zic expression domains overlap with sites of WNT and SHH signaling during otocyst patterning, suggesting a role for Zic genes in modulating signaling from these pathways. ..
- Kordowich S, Collombat P, Mansouri A, Serup P. Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. BMC Dev Biol. 2011;11:52 pubmed publisher..Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in early committed beta-cells. ..
- Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Jing N, Kondoh H. Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. Mol Cell Biol. 2004;24:8834-46 pubmed..Evidence also suggests that such interactions are involved in the regulation of neural primordial cells. ..
- Hara Y, Rovescalli A, Kim Y, Nirenberg M. Structure and evolution of four POU domain genes expressed in mouse brain. Proc Natl Acad Sci U S A. 1992;89:3280-4 pubmed..Additional duplications of the ancestral class III POU domain gene (or mRNA) would create the Brain-1, Brain-2, Brain-4, and Scip genes. ..
- Nakano Y, Kim S, Kim H, Sanneman J, Zhang Y, Smith R, et al. A claudin-9-based ion permeability barrier is essential for hearing. PLoS Genet. 2009;5:e1000610 pubmed publisher..cultured in a low-K+ milieu and in vivo when the endocochlear K+-driving force was diminished by deletion of the pou3f4 gene...
- Yang Y, Magnuson M, Stein R, Wright C. The mammal-specific Pdx1 Area II enhancer has multiple essential functions in early endocrine cell specification and postnatal Î²-cell maturation. Development. 2017;144:248-257 pubmed publisher..Therefore, trans-regulatory integration through Area II mediates a surprisingly extensive range of progenitor and Î²-cell-specific Pdx1 functions. ..
- Du A, Hunter C, Murray J, Noble D, Cai C, Evans S, et al. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes. 2009;58:2059-69 pubmed publisher..These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. ..
- Wang W, Lufkin T. The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Dev Biol. 2000;227:432-49 pubmed..In contrast, the regulation of Brn4 which is also expressed in the SON and PVN is independent of Otp function...
- Sumiyama K, Washio Watanabe K, Saitou N, Hayakawa T, Ueda S. Class III POU genes: generation of homopolymeric amino acid repeats under GC pressure in mammals. J Mol Evol. 1996;43:170-8 pubmed..Those amino acids were encoded by triplet codons with relatively high GC content. These results suggest that the GC pressure has facilitated generation of the homopolymeric amino acid repeats. ..
- Treier M, O Connell S, Gleiberman A, Price J, Szeto D, Burgess R, et al. Hedgehog signaling is required for pituitary gland development. Development. 2001;128:377-86 pubmed..Thus, SHH appears to exert effects on both proliferation and cell-type determination in pituitary gland development. ..
- Jensen J, Heller R, Funder Nielsen T, Pedersen E, Lindsell C, Weinmaster G, et al. Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation. Diabetes. 2000;49:163-76 pubmed..Dynamic expression of Notch1 in PDX+ epithelial cells suggests that Notch signaling could inhibit a Ngn-NeuroD cascade as seen in the nervous system and thus prevent premature differentiation of endocrine cells. ..
- Mastracci T, Wilcox C, Arnés L, Panea C, Golden J, MAY C, et al. Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. Dev Biol. 2011;359:1-11 pubmed publisher..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells. ..
- Gómez López S, Wiskow O, Favaro R, Nicolis S, Price D, Pollard S, et al. Sox2 and Pax6 maintain the proliferative and developmental potential of gliogenic neural stem cells In vitro. Glia. 2011;59:1588-99 pubmed publisher..Overall these findings indicate that Sox2 and Pax6 are both critical for self-renewal of differentiation-competent radial glia-like NS cells. ..
- Xia Y, Andersen B, Mehrabian M, Diep A, Warden C, Mohandas T, et al. Chromosomal organization of mammalian POU domain factors. Genomics. 1993;18:126-30 pubmed..Some of these newly localized genes map in close proximity to existing mouse mutations. ..
- Avraham K, Cho B, Gilbert D, Fujii H, Okamoto K, Shimazaki T, et al. Murine chromosomal location of four class III POU transcription factors. Genomics. 1993;18:131-3 pubmed..Chromosomal mapping has demonstrated that the four genes are unlinked: Otf-6 is located on the distal region of chromosome 4, Otf-7 on the proximal region of chromosome 4, Otf-8 on chromosome 1, and Otf-9 on the X chromosome. ..
- Wilcox C, Terry N, MAY C. Arx polyalanine expansion in mice leads to reduced pancreatic ?-cell specification and increased ?-cell death. PLoS ONE. 2013;8:e78741 pubmed publisher..Overall, our analysis of an Arx polyalanine expansion mutation on pancreatic development suggests that impaired ?-cell function might also occur in ISSX patients. ..
- Dames P, Puff R, Weise M, Parhofer K, Goke B, Gotz M, et al. Relative roles of the different Pax6 domains for pancreatic alpha cell development. BMC Dev Biol. 2010;10:39 pubmed publisher..This function is differentially affected by the two homeodomain mutations analyzed in this study. ..
- Iglesias J, Barg S, Vallois D, Lahiri S, Roger C, Yessoufou A, et al. PPARÎ²/Î´ affects pancreatic Î² cell mass and insulin secretion in mice. J Clin Invest. 2012;122:4105-17 pubmed publisher..Taken together, these results provide evidence for a repressive role for PPARÎ²/Î´ in Î² cell mass and insulin exocytosis, and shed a new light on PPARÎ²/Î´ metabolic action. ..
- Setoguchi R, Kinashi T, Sagara H, Hirosawa K, Takatsu K. Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice. Immunol Lett. 1998;64:109-18 pubmed..Cross-linking of the high affinity IgE receptor (Fc epsilonRI) and steel factor (SLF) induced indistinguishable adhesive responses of mast cells to fibronectin in kinetics, and these adhesive ..
- Sornson M, Wu W, Dasen J, Flynn S, Norman D, O Connell S, et al. Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature. 1996;384:327-33 pubmed..These results imply that a cascade of tissue-specific regulators is responsible for the determination and differentiation of specific cell lineages in pituitary organogenesis. ..
- Iwafuchi Doi M, Matsuda K, Murakami K, Niwa H, Tesar P, Aruga J, et al. Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells. Development. 2012;139:3926-37 pubmed publisher..The direct interaction of these factors with enhancers of Otx2, Hesx1 and Sox2 genes was demonstrated. Thus, a combination of regulatory processes that suppresses non-ANP lineages and promotes neural plate development determines the ANP...
- Jones S, Johnson K, Yu H, Erway L, Alagramam K, Pollak N, et al. A quantitative survey of gravity receptor function in mutant mouse strains. J Assoc Res Otolaryngol. 2005;6:297-310 pubmed..Interestingly, some heterozygote groups also showed abnormalities in one or more VsEP response parameters, suggesting that vestibular dysfunction, although less severe, may be present in some heterozygous animals. ..
- Li F, Su Y, Cheng Y, Jiang X, Peng Y, Li Y, et al. Conditional deletion of Men1 in the pancreatic Î²-cell leads to glucagon-expressing tumor development. Endocrinology. 2015;156:48-57 pubmed publisher..and expressed the mature Î±-cell-specific transcription factors Brain-specific homeobox POU domain protein 4 (Brn4) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MafB)...
- Soto H, Wang W, Strieter R, Copeland N, Gilbert D, Jenkins N, et al. The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3. Proc Natl Acad Sci U S A. 1998;95:8205-10 pubmed..Its ability to attract T cells as well as its angiostatic properties suggest that 6Ckine may be an effective anti-tumor agent. ..
- Braunstein E, Monks D, Aggarwal V, Arnold J, Morrow B. Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis. BMC Dev Biol. 2009;9:31 pubmed publisher..Expression of the mesenchyme marker Brn4 was also lost in the TCre-KO. Brn4-;Tbx1+/-embryos displayed defects in growth of the distal cochlea...
- Dasen J, O Connell S, Flynn S, Treier M, Gleiberman A, Szeto D, et al. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell. 1999;97:587-98 pubmed
- Castro D, Skowronska Krawczyk D, Armant O, Donaldson I, Parras C, Hunt C, et al. Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif. Dev Cell. 2006;11:831-44 pubmed..We thus propose that Mash1 synergizes with Brn factors to regulate multiple steps of neurogenesis. ..
- Dominov J, Miller J. POU homeodomain genes and myogenesis. Dev Genet. 1996;19:108-18 pubmed
- Malik K, Jaffe H, Brady J, Young W. The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U. Brain Res Mol Brain Res. 1997;45:99-107 pubmed..This result suggests another mechanism by which a POU protein can influence gene expression: by facilitating the processing of pre-mRNA whose transcription it has stimulated. ..
- Huh S, Warchol M, Ornitz D. Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling. elife. 2015;4: pubmed publisher..These data define a feedback mechanism, originating from epithelial FGF ligands and mediated through periotic mesenchyme that controls the number of sensory progenitors and the length of the cochlea. ..
- Douville P, Atanasoski S, Tobler A, Fontana A, Schwab M. The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes. Mamm Genome. 1994;5:180-2 pubmed
- Vincent M, Guz Y, Rozenberg M, Webb G, Furuta M, Steiner D, et al. Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis. Endocrinology. 2003;144:4061-9 pubmed..These results indicate that hormones processed by PC2 affected processes that regulate islet cell differentiation and maturation in embryos and adults. ..
- Hussain M, Miller C, Habener J. Brn-4 transcription factor expression targeted to the early developing mouse pancreas induces ectopic glucagon gene expression in insulin-producing beta cells. J Biol Chem. 2002;277:16028-32 pubmed..The early developmental expression of Brn-4 appears to be a dominant regulator of the glucagon expressing alpha cell lineage, even in the context of the beta cell lineage. ..
- Yang Y, Thorel F, Boyer D, Herrera P, Wright C. Context-specific ?- to-?-cell reprogramming by forced Pdx1 expression. Genes Dev. 2011;25:1680-5 pubmed publisher..Our findings reveal that Pdx1 can work single-handedly as a potent context-dependent autonomous reprogramming agent, and suggest a postnatal differentiation evaluation stage involved in normal endocrine maturation. ..
- Treier M, Gleiberman A, O Connell S, Szeto D, McMahon J, McMahon A, et al. Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev. 1998;12:1691-704 pubmed
- Parzefall T, Shivatzki S, Lenz D, Rathkolb B, Ushakov K, Karfunkel D, et al. Cytoplasmic mislocalization of POU3F4 due to novel mutations leads to deafness in humans and mice. Hum Mutat. 2013;34:1102-10 pubmed publisherb>POU3F4 is a POU domain transcription factor that is required for hearing. In the ear, POU3F4 is essential for mesenchymal remodeling of the bony labyrinth and is the causative gene for DFNX2 human nonsyndromic deafness...
- Kioussi C, O Connell S, St Onge L, Treier M, Gleiberman A, Gruss P, et al. Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc Natl Acad Sci U S A. 1999;96:14378-82 pubmed..We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals. ..
- Shimazaki T, Arsenijevic Y, Ryan A, Rosenfeld M, Weiss S. A role for the POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation. EMBO J. 1999;18:444-56 pubmed..These findings suggest that Brn-4 mediates, at least in part, the actions of epigenetic signals that induce striatal neuron-precursor differentiation. ..
- Watanabe M, Akiyama N, Hasegawa N, Manome Y. Progressive degeneration of stereocilia in cochlear hair cells in hearing-impaired kuru2 mice. In Vivo. 2005;19:675-81 pubmed
- Ekonomou A, Kazanis I, Malas S, Wood H, Alifragis P, Denaxa M, et al. Neuronal migration and ventral subtype identity in the telencephalon depend on SOX1. PLoS Biol. 2005;3:e186 pubmed..Our data also suggest that other SOXB1 members showing expression in specific neuronal populations are likely to play continuous roles from the establishment of precursors to their final differentiation. ..