The basic objective of our laboratory effort has been, and continues to be, the characterization of basic developmental processes involved in normal craniofacial morphogenesis to enable identification of the causes of abnormal development. Our research strategy involves an approach to the etiology of congenital craniofacial dysmorphology from the standpoint of cellular and developmental biology. The rational elimination of teratogenic influences in human facial development requires a clear understanding of the biology of normal craniofacial ontogeny. Progress during the previous funding period has demonstrated that several molecular species (prostaglandins, catecholamines) shown to be present in the developing orofacial region, act in a receptor mediated fashion to modulate proliferation of embryonic palate mesenchymal cells by alteration of intracellular levels of cAMP. Studies outlined in the current application involve analysis of intracellular transduction mechanisms which mediate cAMP-induced biological responses to hormone and growth factor stimulation. We propose to investigate intracellular effectors (ornithine decarboxylase, cAMP-dependent protein kinase) by which secondary messengers (cAMP, Ca2+) evoke a developmentally significant biological response (growth, glycosaminoglycan synthesis) in embryonic palatal tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE005550-09
Application #
3219478
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1981-02-01
Project End
1990-07-31
Budget Start
1989-02-01
Budget End
1990-07-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Mukhopadhyay, Partha; Greene, Robert M; Pisano, M Michele (2015) Cigarette smoke induces proteasomal-mediated degradation of DNA methyltransferases and methyl CpG-/CpG domain-binding proteins in embryonic orofacial cells. Reprod Toxicol 58:140-8
Warner, Dennis R; Mukhopadhyay, Partha; Brock, Guy et al. (2014) MicroRNA expression profiling of the developing murine upper lip. Dev Growth Differ 56:434-47
Mukhopadhyay, Partha; Brock, Guy; Appana, Savitri et al. (2011) MicroRNA gene expression signatures in the developing neural tube. Birth Defects Res A Clin Mol Teratol 91:744-62
Warner, Dennis R; Mukhopadhyay, Partha; Brock, Guy N et al. (2011) TGF?-1 and Wnt-3a interact to induce unique gene expression profiles in murine embryonic palate mesenchymal cells. Reprod Toxicol 31:128-33
Greene, Robert M; Pisano, M Michele (2010) Palate morphogenesis: Current understanding and future directions. Birth Defects Res C Embryo Today 90:133-54
Mukhopadhyay, Partha; Rezzoug, Francine; Webb, Cynthia L et al. (2009) Suppression of chondrogenesis by Id helix-loop-helix proteins in murine embryonic orofacial tissue. Differentiation 77:462-72
Warner, Dennis R; Smith, Henry S; Webb, Cynthia L et al. (2009) Expression of Wnts in the developing murine secondary palate. Int J Dev Biol 53:1105-12
Mukhopadhyay, Partha; Webb, Cynthia L; Warner, Dennis R et al. (2008) BMP signaling dynamics in embryonic orofacial tissue. J Cell Physiol 216:771-9
Yin, Xiaolong; Warner, Dennis R; Roberts, Emily A et al. (2005) Identification of novel CBP interacting proteins in embryonic orofacial tissue. Biochem Biophys Res Commun 329:1010-7
Weston, W M; Greene, R M; Uberti, M et al. (1994) Ethanol effects on embryonic craniofacial growth and development: implications for study of the fetal alcohol syndrome. Alcohol Clin Exp Res 18:177-82

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