Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse
The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3). However, the target genes and developmental processes controlled by POU3F4 transcription factor activity ha...
| Main Authors: | , , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Public Library of Science
2014
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192298/ |
| id |
pubmed-4192298 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-41922982014-10-14 Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse Raft, Steven Coate, Thomas M. Kelley, Matthew W. Crenshaw, E. Bryan Wu, Doris K. Research Article The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3). However, the target genes and developmental processes controlled by POU3F4 transcription factor activity have remained largely uncharacterized. Ephrin-B2 (Efnb2) is a signaling molecule with well-documented effects on cell adhesion, proliferation, and migration. Our analyses of targeted mouse mutants revealed that Efnb2 loss-of-function phenocopies temporal bone abnormalities of Pou3f4 hemizygous null neonates: qualitatively identical malformations of the stapes, styloid process, internal auditory canal, and cochlear capsule were present in both mutants. Using failed/insufficient separation of the stapes and styloid process as a quantitative trait, we found that single gene Efnb2 loss-of-function and compound Pou3f4/Efnb2 loss-of-function caused a more severe phenotype than single gene Pou3f4 loss-of-function. Pou3f4 and Efnb2 gene expression domains overlapped at the site of impending stapes-styloid process separation and at subcapsular mesenchyme surrounding the cochlea; at both these sites, Efnb2 expression was attenuated in Pou3f4 hemizygous null mutants relative to control. Results of immunoprecipitation experiments using chromatin isolated from nascent middle ear mesenchyme supported the hypothesis of a physical association between Pou3f4 and specific non-coding sequence of Efnb2. We propose that Efnb2 is a target of Pou3f4 transcription factor activity and an effector of mesenchymal patterning during temporal bone development. Public Library of Science 2014-10-09 /pmc/articles/PMC4192298/ /pubmed/25299585 http://dx.doi.org/10.1371/journal.pone.0109043 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Raft, Steven Coate, Thomas M. Kelley, Matthew W. Crenshaw, E. Bryan Wu, Doris K. |
| spellingShingle |
Raft, Steven Coate, Thomas M. Kelley, Matthew W. Crenshaw, E. Bryan Wu, Doris K. Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse |
| author_facet |
Raft, Steven Coate, Thomas M. Kelley, Matthew W. Crenshaw, E. Bryan Wu, Doris K. |
| author_sort |
Raft, Steven |
| title |
Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse |
| title_short |
Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse |
| title_full |
Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse |
| title_fullStr |
Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse |
| title_full_unstemmed |
Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone Development in the Mouse |
| title_sort |
pou3f4-mediated regulation of ephrin-b2 controls temporal bone development in the mouse |
| description |
The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3). However, the target genes and developmental processes controlled by POU3F4 transcription factor activity have remained largely uncharacterized. Ephrin-B2 (Efnb2) is a signaling molecule with well-documented effects on cell adhesion, proliferation, and migration. Our analyses of targeted mouse mutants revealed that Efnb2 loss-of-function phenocopies temporal bone abnormalities of Pou3f4 hemizygous null neonates: qualitatively identical malformations of the stapes, styloid process, internal auditory canal, and cochlear capsule were present in both mutants. Using failed/insufficient separation of the stapes and styloid process as a quantitative trait, we found that single gene Efnb2 loss-of-function and compound Pou3f4/Efnb2 loss-of-function caused a more severe phenotype than single gene Pou3f4 loss-of-function. Pou3f4 and Efnb2 gene expression domains overlapped at the site of impending stapes-styloid process separation and at subcapsular mesenchyme surrounding the cochlea; at both these sites, Efnb2 expression was attenuated in Pou3f4 hemizygous null mutants relative to control. Results of immunoprecipitation experiments using chromatin isolated from nascent middle ear mesenchyme supported the hypothesis of a physical association between Pou3f4 and specific non-coding sequence of Efnb2. We propose that Efnb2 is a target of Pou3f4 transcription factor activity and an effector of mesenchymal patterning during temporal bone development. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192298/ |
| _version_ |
1613142834372673536 |