This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term objectives of this proposal are to clarify the role of microRNAs and their target genes during mammalian orofacial development. Formation of the mammalian orofacial tissue is a complex, coordinated developmental process involving cell migration, proliferation, differentiation, apoptosis, and synthesis of extracellular matrix. All these critical cellular processes are believed to be under the control of numerous microRNAs (miRNAs) and their target genes encoding growth and differentiation factors, signaling mediators, transcription factors and extracellular matrix proteins. Disruptions in any one of these processes can lead to orofacial clefting. Emerging evidences strongly support central roles for miRNAs in orofacial ontogenesis. Our preliminary data demonstrated that a panoply of miRNA- and protein-coding genes are differentially expressed during the crucial period of orofacial development. Bioinformatic analysis revealed identification of several target genes (of those miRNAs) many of which have documented critical roles in orofacial morphogenesis. Furthermore, pathway analysis enabled identification of important biological pathways or gene interaction networks involving the miRNAs and their target genes, as well as linking vital cellular processes governing growth of the embryonic orofacial region. We thus propose to test the hypothesis that interaction between differentially-expressed miRNAs and their target mRNAs are essential for proper development of the embryonic orofacial region. Three hypothesis-driven specific aims will be pursued: 1) Within the developing orofacial tissue several differentially expressed genes encoding mRNAs are targets of miRNAs differentially expressed in that tissue. 2) Interaction between differentially-expressed miRNAs and mRNAs are essential for the regulation of specific biological processes as well as phenotypic outcomes associated with orofacial development. 3) Overexpression or inhibition of expression of discrete miRNAs modulates the expression of their target genes which in turn affects the cellular processes indispensable for the morphogenesis of the orofacial region.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017702-09
Application #
8360174
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
9
Fiscal Year
2011
Total Cost
$103,710
Indirect Cost
Name
University of Louisville
Department
Dentistry
Type
Schools of Dentistry
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Mukhopadhyay, Partha; Seelan, Ratnam S; Rezzoug, Francine et al. (2017) Determinants of orofacial clefting I: Effects of 5-Aza-2'-deoxycytidine on cellular processes and gene expression during development of the first branchial arch. Reprod Toxicol 67:85-99
Liu, Xiao; Tang, Luosheng; Liu, Yongqing (2017) Mouse Müller Cell Isolation and Culture. Bio Protoc 7:
Li, Shengqiang; Moore, Andrew K; Zhu, Jia et al. (2016) Ggnbp2 Is Essential for Pregnancy Success via Regulation of Mouse Trophoblast Stem Cell Proliferation and Differentiation. Biol Reprod 94:41
Neal, Rachel E; Chen, Jing; Webb, Cindy et al. (2016) Developmental cigarette smoke exposure II: Hepatic proteome profiles in 6 month old adult offspring. Reprod Toxicol 65:414-424
Neal, Rachel E; Jagadapillai, Rekha; Chen, Jing et al. (2016) Developmental cigarette smoke exposure II: Kidney proteome profile alterations in 6 month old adult offspring. Reprod Toxicol 65:425-435
Warner, Dennis R; Smith, Scott C; Smolenkova, Irina A et al. (2016) Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression. Exp Cell Res 342:32-8
Neal, Rachel E; Jagadapillai, Rekha; Chen, Jing et al. (2016) Developmental cigarette smoke exposure II: Hippocampus proteome and metabolome profiles in adult offspring. Reprod Toxicol 65:436-447
Cashon, Cara H; Ha, Oh-Ryeong; Graf Estes, Katharine et al. (2016) Infants with Williams syndrome detect statistical regularities in continuous speech. Cognition 154:165-168
Jin, Jiu-Zhen; Ding, Jixiang (2015) Strain-Dependent Gene Expression during Mouse Embryonic Palate Development. J Dev Biol 3:2-10
Warner, Dennis; Ding, Jixiang; Mukhopadhyay, Partha et al. (2015) Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgf?3(-/-) Mouse Fetuses. Microrna 4:64-71

Showing the most recent 10 out of 111 publications