Pou3f4 deficiency causes defects in otic fibrocytes and stria vascularis by different mechanisms

Song, Mee Hyun; Choi, Soo‐Young; Wu, Ling; Oh, Se-Kyoung; Lee, Hee Keun; Lee, Dong Jin; Shim, Dae-Bo; Choi, Jae Young; Kim, Un-Kyung; Bok, Jinwoong

doi:10.1016/j.bbrc.2010.12.019

Cited by 27 publications

(27 citation statements)

References 28 publications

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“…Most of these mutations are within the regions that encode the DNA-binding domains of Oct9, and thus, these mutations can severely affect Oct9 DNA binding and its capacity to transactivate target genes (95, 96) such as Epha4 in optic mesenchyme cells (191). The hearing loss associated with nonfunctional Oct9 in humans is consistent with observations in Oct9-deficient mice, which reveal defective otic fibrocytes and stria vascularis in the cochlear lateral wall (192, 193). …”

Section: Pathophysiological Roles Of Oct Proteinssupporting

confidence: 85%

Octamer-binding transcription factors: genomics and functions

Zhao¹

2013

Front Biosci

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The Octamer-binding proteins (Oct) are a group of highly conserved transcription factors that specifically bind to the octamer motif (ATGCAAAT) and closely related sequences that are found in promoters and enhancers of a wide variety of both ubiquitously expressed and cell type-specific genes. Oct factors belong to the larger family of POU domain factors that are characterized by the presence of a highly conserved bipartite DNA binding domain, consisting of an amino-terminal specific subdomain (POUS) and a carboxyl-terminal homeo-subdomain (POUH). Eleven Oct proteins have been named (Oct1-11), and currently, eight genes encoding Oct proteins (Oct1, Oct2, Oct3/4, Oct6, Oct7, Oct8, Oct9, and Oct11) have been cloned and characterized. Oct1 and Oct2 are widely expressed in adult tissues, while other Oct proteins are much more restricted in their expression patterns. Oct proteins are implicated in crucial and versatile biological events, such as embryogenesis, neurogenesis, immunity, and body glucose and amino acid metabolism. The aberrant expression and null function of Oct proteins have also been linked to various diseases, including deafness, diabetes and cancer. In this review, I will report both the genomic structure and major functions of individual Oct proteins in physiological and pathological processes.

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Section: Pathophysiological Roles Of Oct Proteinssupporting

confidence: 85%

Octamer-binding transcription factors: genomics and functions

Zhao¹

2013

Front Biosci

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“…11D) or Pou3f4 (Supplementary Fig. 12D,E), which is widely expressed in the otic mesenchyme343536, demonstrating that the multipotent stem/progenitors do not originate from the otic ectoderm-derived Neurod1 + lineage committed progenitors or Pou3f4 + otic mesenchyme. Thus our analyses identify a previously unknown population of multipotent stem/progenitor cells that share some characteristics with glial cells that originate from Eya1 -expressing cells.…”

Section: Resultsmentioning

confidence: 95%

Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti

Ueno

et al. 2017

Nat Commun

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The adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage. These multipotent progenitors originate from Eya1-expressing otic progenitors. Our findings also provide evidence for detectable regenerative potential in the postnatal cochlea beyond 1 week of age.

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“…Currently, the downstream targets of POU3F4, including gap junction genes and their proposed transcription factors in the cochlear supporting cells, are unknown. Only a few genes have been reported to be involved in fibrocyte differentiation including Otospiralin (Otos) [13] and Tbx18 [14], although Song et al reported that neither Otos nor Tbx18 expression was affected in the spiral ligament of Brn4-deficient mice [15]. Although the entire molecular pathway between Brn4 and the cochlear gap junction has not yet been worked out, our data clearly demonstrated that POU3F4 affects the expression and assembly of the gap junction proteins Cx30 (GJB6) and Cx26 (GJB2) in cochlear supporting cells.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Transcription Factor Brn4 Disrupts Cochlear Gap Junction Plaques in a Model of DFN3 Non-Syndromic Deafness

et al. 2014

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Brn4, which encodes a POU transcription factor, is the gene responsible for DFN3, an X chromosome–linked, non-syndromic type of hearing loss. Brn4-deficient mice have a low endocochlear potential (EP), hearing loss, and ultrastructural alterations in spiral ligament fibrocytes, however the molecular pathology through which Brn4 deficiency causes low EP is still unclear. Mutations in the Gjb2 and Gjb6 genes encoding the gap junction proteins connexin26 (Cx26) and connexin30 (Cx30) genes, respectively, which encode gap junction proteins and are expressed in cochlear fibrocytes and non-sensory epithelial cells (i.e., cochlear supporting cells) to maintain the proper EP, are responsible for hereditary sensorineural deafness. It has been hypothesized that the gap junction in the cochlea provides an intercellular passage by which K+ is transported to maintain the EP at the high level necessary for sensory hair cell excitation. Here we analyzed the formation of gap junction plaques in cochlear supporting cells of Brn4-deficient mice at different stages by confocal microscopy and three-dimensional graphic reconstructions. Gap junctions from control mice, which are composed mainly of Cx26 and Cx30, formed linear plaques along the cell-cell junction sites with adjacent cells. These plaques formed pentagonal or hexagonal outlines of the normal inner sulcus cells and border cells. Gap junction plaques in Brn4-deficient mice did not, however, show the normal linear structure but instead formed small spots around the cell-cell junction sites. Gap junction lengths were significantly shorter, and the level of Cx26 and Cx30 was significantly reduced in Brn4-deficient mice compared with littermate controls. Thus the Brn4 mutation affected the assembly and localization of gap junction proteins at the cell borders of cochlear supporting cells, suggesting that Brn4 substantially contributes to cochlear gap junction properties to maintain the proper EP in cochleae, similar to connexin-related deafness.

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Pou3f4 deficiency causes defects in otic fibrocytes and stria vascularis by different mechanisms

Cited by 27 publications

References 28 publications

Octamer-binding transcription factors: genomics and functions

Octamer-binding transcription factors: genomics and functions

Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti

Deficiency of Transcription Factor Brn4 Disrupts Cochlear Gap Junction Plaques in a Model of DFN3 Non-Syndromic Deafness

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