Changes in the subcellular localization of the Brn4 gene product precede mesenchymal remodeling of the otic capsule

Phippard, Deborah; Heydemann, Ahlke; Lechner, Mark S.; Lü, Lihui; Lee, Daniel; Kyin, Tim; Crenshaw, E. Bryan

doi:10.1016/s0378-5955(98)00059-8

Cited by 65 publications

(70 citation statements)

References 21 publications

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“…Seven micrometer thick sections were treated with either polyclonal rabbit antiTbx1 serum (Zymed) 1:500, affinity-purified rabbit polyclonal anti-Brn4 Ab (Phippard et al 1998) 1:400, anti-cleaved Caspase 3 (R&D Systems) 1:1,000, or antiphospho-Histone 3 (Upstate) 1:200 in TBS/0.1% Triton X-100/5% goat serum/2%BSA. Sections were incubated for 1 h at room temperature and visualized with a biotinylated goat anti-rabbit IgG conjugate (1:200; DakoCytomation), avidin-biotin complex/HRP formation (DakoCytomation) and DAB/chromogen reaction (DakoCytomation).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Cooperative Function of Tbx1 and Brn4 in the Periotic Mesenchyme is Necessary for Cochlea Formation

Braunstein

Crenshaw

Morrow

et al. 2008

JARO

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The T-box transcription factor TBX1 has been identified as the major gene responsible for the etiology of velocardiofacial syndrome/DiGeorge syndrome (VCFS/DGS). Conductive hearing loss occurs in a majority of patients with this syndrome, while sensorineural deafness has also been reported in some cases. Mutations in POU3F4/BRN4, a POU domain transcription factor, cause DFN3, an X-linked nonsyndromic form of deafness characterized by mixed conductive and sensorineural hearing loss. Inactivation of the murine orthologues of these genes causes similar defects to those seen in humans and has provided excellent models for the study of inner ear development. Tbx1 and Brn4 are expressed in the mesenchymal cells surrounding the otic vesicle and have been shown to play roles in cochlear outgrowth. Furthermore, expression of Brn4 is reduced in Tbx1 null mutants, suggesting a possible genetic interaction between these genes. To test whether Tbx1 and Brn4 function in a common pathway, mice mutant for both genes were generated and analyzed for inner ear defects. Brn4−;Tbx1+/− mutants displayed a significant reduction in the number of turns of the cochlea compared to Brn4− or Tbx1+/− mice. In addition, Brn4−;Tbx1+/− mice displayed structural defects in the apical cochlea indicative of Mondini dysplasia found in patients with either VCFS/DGS or DFN3. These data establish a genetic interaction between Tbx1 and Brn4 relevant to human disease and indicate a function of these genes in signaling from the periotic mesenchyme to the otic vesicle to direct proper coiling of the cochlear duct.

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Section: Immunohistochemistrymentioning

confidence: 99%

“…Brn4 is not expressed in the otic vesicle but is expressed throughout the periotic mesenchyme (Phippard et al 1998). Mice null for Brn4 exhibit profound hearing loss due to a reduction in endocochlear potential (Minowa et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Cooperative Function of Tbx1 and Brn4 in the Periotic Mesenchyme is Necessary for Cochlea Formation

Braunstein

Crenshaw

Morrow

et al. 2008

JARO

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“…Brn4 (Pou3f4), a transcription factor belonging to the POU-domain gene family, is expressed in the periotic mesenchyme (Phippard et al 1998). Knockout mice of Brn4 are deaf, and vestibular phenotypes such as head bobbing have been reported in one of the two knockout lines (Minowa et al 1999;Phippard et al 1999).…”

Section: Genes Expressed In the Mesenchymementioning

confidence: 99%

Molecular Genetics of Vestibular Organ Development

Chang¹,

Cole²,

Cantos³

et al. 2004

The Vestibular System

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“…Phippard et al [5] addressed this malformation as pseudo Mondini stage II, described as partial hypoplasia of the cochlea, stapes fixation, dilated IAC and abnormal communication with the base of the cochlear duct. Sennaroglu and Saatci [6] described a new classification in 2002.…”

Section: Discussionmentioning

confidence: 99%

Cochlear implantation: case report on incomplete partition type III

Özcan¹

2017

Kulak Burun Bogaz Ihtis Derg

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Incomplete partition (IP) type III anomaly (X-linked deformity, IP type III) is a rare malformation of the inner ear. In these patients, cochlear implant surgery can be performed successfully. In this case report, we discussed the problems regarding cochlear implantation in patients with IP type III anomaly and profound sensorineural hearing loss. Cochlear implantation is a good choice for these patients. However, IP type III anomaly may pose some unusual risks in addition to other inner ear abnormalities. Therefore, the surgeon should be aware of these and must be ready to inform the patient and parents about possible complications.Keywords: Cochlear implant; incomplete partition type III anomaly; inner ear anomaly. ÖZİnkomplet partisyon (İP) tip III anomalisi (X-bağımlı deformite, İP tip III) iç kulağın nadir bir malformasyonudur. Bu hastalarda koklear implant cerrahisi başarıyla uygulanabilir. Bu olgu sunumunda, İP tip III anomalisi ve şiddetli sensörinöral işitme kaybı olan hastalarda koklear implantasyon ile ilgili problemler tartışıldı. Koklear implantasyon bu hastalar için iyi bir tercihtir. Ancak İP tip III anomalisi diğer iç kulak anormalliklerine ek olarak bazı olağandışı riskler oluşturabilir. Dolayısıyla, cerrah bunları bilmeli ve hastayı ve ebeveynleri olası komplikasyonlar hakkında bilgilendirmeye hazır olmalıdır.Anahtar Sözcükler: Koklear implant; inkomplet partisyon tip III anomalisi; iç kulak anomalisi.

show abstract

Changes in the subcellular localization of the Brn4 gene product precede mesenchymal remodeling of the otic capsule

Cited by 65 publications

References 21 publications

Cooperative Function of Tbx1 and Brn4 in the Periotic Mesenchyme is Necessary for Cochlea Formation

Cooperative Function of Tbx1 and Brn4 in the Periotic Mesenchyme is Necessary for Cochlea Formation

Molecular Genetics of Vestibular Organ Development

Cochlear implantation: case report on incomplete partition type III

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