This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 #
5P20RR017702-08
Application #
8167652
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2010-06-01
Project End
2011-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
8
Fiscal Year
2010
Total Cost
$169,988
Indirect Cost
Name
University of Louisville
Department
Dentistry
Type
Schools of Dentistry
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Jin, Jiu-Zhen; Lei, Zhenmin; Lan, Zi-Jian et al. (2018) Inactivation of Fgfr2 gene in mouse secondary palate mesenchymal cells leads to cleft palate. Reprod Toxicol 77:137-142
Liu, Lingyun; He, Yan; Guo, Kaimin et al. (2017) Ggnbp2-Null Mutation in Mice Leads to Male Infertility due to a Defect at the Spermiogenesis Stage. Am J Pathol 187:2508-2519
Liu, Xiao; Tang, Luosheng; Liu, Yongqing (2017) Mouse Müller Cell Isolation and Culture. Bio Protoc 7:
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
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
Lan, Zi-Jian; Hu, YunHui; Zhang, Sheng et al. (2016) GGNBP2 acts as a tumor suppressor by inhibiting estrogen receptor ? activity in breast cancer cells. Breast Cancer Res Treat 158:263-76
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

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