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. Cleft palate is a common birth defect caused by malformation in secondary palate development. Palate formation requires signaling pathways to function interactively rather than in isolation. However, our understanding of the signaling networks during palate fusion, growth and elevation remains poor. The proposed research will focus on the interactions among major signaling pathways during palate development. TGF-?3 is an essential signaling molecule mediating palate fusion, but the mechanism of action is unknown. We found that TGF-?3 is required for the down-regulation of Jag2 expression during fusion, suggesting TGF-? and Notch pathways function synergistically during fusion. Jag2, IRF6 and IKKa are key regulator factors in preventing pathogenic palate fusion with the tongue and other tissues, and recent studies have revealed the integration of these factors in controlling palate adhesion and fusion. We will pursue two specific aims: I) Interactions between TGF-?3, Notch1/Jag2 during normal and pathogenic palate fusion. We will 1) take a genetic approach to test the hypothesis that TGF-?3 mediates palate fusion by down-regulating Jag2 expression in the MEE;2) investigate the functional significance of Jag2 down-regulation in MEE during wild type palate fusion. II) Investigation of TGF-? signaling and its interaction with Wnt5a during palate elevation. We will 1) investigate the downstream target genes of Zfhx1a during palate elevation focusing on the genes involving cell migration;2) investigation of the function of TGF-?1,2 during palate by generating TGF-?1,2 double mutants;3) examine the effects of TGF-?s on Wnt5a mediated non-canonical signaling.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017702-09
Application #
8360169
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
$168,532
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

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