<it>Tbx1 </it>and <it>Brn4 </it>regulate retinoic acid metabolic genes during cochlear morphogenesis

• Main Authors: Braunstein Evan M, Monks Dennis C, Aggarwal Vimla S, Arnold Jelena S, Morrow Bernice E
• Format: Article
• Language: English
• Published: BMC 2009-05-01
• Series: BMC Developmental Biology
• Online Access: http://www.biomedcentral.com/1471-213X/9/31

<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>^-;<it>Tbx1</it>^+/-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>^-;<it>Tbx1</it>^+/-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>