Indian Journal of Human Genetics
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ORIGINAL ARTICLE
Year : 2012  |  Volume : 18  |  Issue : 3  |  Page : 310-319

Conditional deletion of the human ortholog gene Dicer1 in Pax2-Cre expression domain impairs orofacial development


1 Department of Oral Biology, Creighton University School of Dentistry, Omaha, NE, USA
2 Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA

Correspondence Address:
Sonia M Rocha-Sanchez
Creighton University School of Dentistry, Department of Oral Biology, Boyne Bldg., Room 313, Omaha, NE-68178
USA
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Source of Support: This work was supported in part by an Oral Biology Faculty Development grant from Health Future Foundation (HFF) (S.M. Rocha-Sanchez), NIH/NIDCD R01DC009025 (G.A. Soukup) and NIH/ NCRR G20RR024001 (Creighton University Animal Research Facility). We thank Ms. Sabrina Siddiqi for valuable technical assistance and Dr. Andy Groves (Baylor College of Medicine) for generously donating the Pax2 and Cre probes. Confocal microscopic system was made available by the Nebraska Center for Cell Biology at Creighton University, Conflict of Interest: None


DOI: 10.4103/0971-6866.107984

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Background: Orofacial clefts are common worldwide and result from insufficient growth and/or fusion during the genesis of the derivatives of the first pharyngeal arch and the frontonasal prominence. Recent studies in mice carrying conditional and tissue-specific deletions of the human ortholog Dicer1, an RNAse III family member, have highlighted its importance in cell survival, differentiation, proliferation, and morphogenesis. Nevertheless, information regarding Dicer1 and its dependent microRNAs (miRNAs) in mammalian palatogenesis and orofacial development is limited. Aims: To describe the craniofacial phenotype, gain insight into potential mechanisms underlying the orofacial defects in the Pax2-Cre/Dicer1 CKO mouse, and shed light on the role of Dicer1 in mammalian palatogenesis. Materials And Methods: Histological and molecular assays of wild type (WT) and Pax2-Cre/Dicer1 loxP/loxP (Dicer1 CKO) mice dissected tissues have been performed to characterize and analyze the orofacial dysmorphism in Pax2-Cre/Dicer1 loxP/loxP mouse. Results: Dicer1 CKO mice exhibit late embryonic lethality and severe craniofacial dysmorphism, including a secondary palatal cleft. Further analysis suggest that Dicer1 deletion neither impacts primary palatal development nor the initial stages of secondary palatal formation. Instead, Dicer1 is implicated in growth, differentiation, mineralization, and survival of cells in the lateral palatal shelves. Histological and molecular analysis demonstrates that secondary palatal development becomes morphologically arrested prior to mineralization around E13.5 with a significant increase in the expression levels of apoptotic markers (P < 0.01). Conclusions: Pax2-Cre-mediated Dicer1 deletion disrupts lateral palatal outgrowth and bone mineralization during palatal shelf development, therefore providing a mammalian model for investigating the role of miRNA-mediated signaling pathways during palatogenesis.


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