<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis
<p>Abstract</p> <p>Background</p> <p>In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. <it>Tbx1</it>, the gene...
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doaj-3331f1e423fa4a7ca30c28fda389e4bd2020-11-24T21:10:34ZengBMCBMC Developmental Biology1471-213X2009-05-01913110.1186/1471-213X-9-31<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesisBraunstein Evan MMonks Dennis CAggarwal Vimla SArnold Jelena SMorrow Bernice E<p>Abstract</p> <p>Background</p> <p>In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. <it>Tbx1</it>, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. <it>Tbx1 </it>is expressed in the otic epithelium and adjacent periotic mesenchyme (POM), and both of these domains are required for inner ear formation. To study the function of <it>Tbx1 </it>in the POM, we have conditionally inactivated <it>Tbx1 </it>in the mesoderm while keeping expression in the otic vesicle intact.</p> <p>Results</p> <p>Conditional mutants (<it>TCre-KO</it>) displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that <it>Tbx1 </it>expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker <it>Brn4 </it>was also lost in the <it>TCre-KO</it>. <it>Brn4</it><sup>-</sup>;<it>Tbx1</it><sup>+/-</sup>embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA) catabolizing genes was examined in both mutants. <it>Cyp26a1 </it>expression was altered in the <it>TCre-KO</it>, while <it>Cyp26c1 </it>showed reduced expression in both <it>TCre-KO </it>and <it>Brn4</it><sup>-</sup>;<it>Tbx1</it><sup>+/- </sup>embryos.</p> <p>Conclusion</p> <p>These results indicate that <it>Tbx1 </it>expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.</p> http://www.biomedcentral.com/1471-213X/9/31 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Braunstein Evan M Monks Dennis C Aggarwal Vimla S Arnold Jelena S Morrow Bernice E |
spellingShingle |
Braunstein Evan M Monks Dennis C Aggarwal Vimla S Arnold Jelena S Morrow Bernice E <it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis BMC Developmental Biology |
author_facet |
Braunstein Evan M Monks Dennis C Aggarwal Vimla S Arnold Jelena S Morrow Bernice E |
author_sort |
Braunstein Evan M |
title |
<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis |
title_short |
<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis |
title_full |
<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis |
title_fullStr |
<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis |
title_full_unstemmed |
<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis |
title_sort |
<it>tbx1 </it>and <it>brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis |
publisher |
BMC |
series |
BMC Developmental Biology |
issn |
1471-213X |
publishDate |
2009-05-01 |
description |
<p>Abstract</p> <p>Background</p> <p>In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. <it>Tbx1</it>, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. <it>Tbx1 </it>is expressed in the otic epithelium and adjacent periotic mesenchyme (POM), and both of these domains are required for inner ear formation. To study the function of <it>Tbx1 </it>in the POM, we have conditionally inactivated <it>Tbx1 </it>in the mesoderm while keeping expression in the otic vesicle intact.</p> <p>Results</p> <p>Conditional mutants (<it>TCre-KO</it>) displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that <it>Tbx1 </it>expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker <it>Brn4 </it>was also lost in the <it>TCre-KO</it>. <it>Brn4</it><sup>-</sup>;<it>Tbx1</it><sup>+/-</sup>embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA) catabolizing genes was examined in both mutants. <it>Cyp26a1 </it>expression was altered in the <it>TCre-KO</it>, while <it>Cyp26c1 </it>showed reduced expression in both <it>TCre-KO </it>and <it>Brn4</it><sup>-</sup>;<it>Tbx1</it><sup>+/- </sup>embryos.</p> <p>Conclusion</p> <p>These results indicate that <it>Tbx1 </it>expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.</p> |
url |
http://www.biomedcentral.com/1471-213X/9/31 |
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