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Publication : Identification of putative retinoic acid target genes downstream of mesenchymal Tbx1 during inner ear development.

First Author  Monks DC Year  2012
Journal  Dev Dyn Volume  241
Issue  3 Pages  563-73
PubMed ID  22275070 Mgi Jnum  J:181273
Mgi Id  MGI:5310683 Doi  10.1002/dvdy.23731
Citation  Monks DC, et al. (2012) Identification of putative retinoic acid target genes downstream of mesenchymal Tbx1 during inner ear development. Dev Dyn 241(3):563-73
abstractText  Background: The T-box transcription factor Tbx1 is expressed in the otic vesicle and surrounding mesoderm of the periotic mesenchyme (POM) during inner ear development. Mesenchymal Tbx1 is essential for inner ear development, with conditional mutants displaying defects in both the auditory and vestibular systems. We have previously reported that mesodermal Tbx1 loss of function mutants (Mest-KO) have reduced expression of retinoic acid (RA) metabolic genes, Cyp26a1 and Cyp26c1, in the POM, consistent with other studies showing an increase in mesodermal RA reporter expression in Tbx1-/- embryos. However, putative RA effector genes whose expression is altered downstream of increased otic mesenchymal-epithelial RA signaling have remained elusive. Results: Here we report the identification of 18 retinoic acid responsive genes altered in Mest-KO conditional mutants by microarray gene profiling. Nine were chosen for biological validation including quantitative RT-PCR and in situ hybridization (Otor, Mia, Col2a1, Clu, Adm, Myt1, Dlx3, Itgb3, and Itga2b). Conclusion: Here study provides a series of newly identified RA effector genes for inner ear development downstream of mesenchymal Tbx1 that may contribute to the inner ear phenotype observed in Tbx1 loss of function mouse models. Developmental Dynamics 241:563-573, 2012. (c) 2012 Wiley Periodicals, Inc.
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