Dennis R. Warner, Ph.D.
Dennis R. Warner, Ph.D.
I – Research narrative
Clefts of the palate are amongst the most prevalent birth defects in humans, found in as many as 1 in 700 births and thus constitute a significant burden upon the health care system. Successful development of early intervention and prevention strategies requires a comprehensive understanding of the regulatory networks that control the cellular processes necessary for proper secondary palate formation. Recently, it was demonstrated that mice lacking the transcriptional co-regulator, PRDM16, have a complete cleft of the secondary palate. The precise mechanism underlying this phenotype, however, is not known. We have previously demonstrated that PRDM16 is a Smad binding protein that can modulate signaling through the TGF-β, and likely the BMP, pathways, both important regulators of palatogenesis. Current studies are being conducted to elucidate the functional consequence for palate development as a result of loss of PRDM16, in addition to the identification of genes regulated by this protein. Other projects have been pursued to characterize the Wnt signaling pathway proteins in the developing palate of embryonic mice. Wnts are a family of secreted cytokines that are important regulators of critical developmental processes such as cell proliferation, cell specification, apoptosis, cell and tissue polarity and their importance during palate development is only now being revealed. We have performed a detailed analysis of the expression pattern of many Wnt proteins in the palates of embryonic mice and found highly specific and unique patterns of expression. These results form the basis of future studies to elaborate the mechanism of action of the various Wnt family members during palate development with an eye toward preventing this common birth defect.
III - Publications
- Warner DR, Mukhopadhyay P, Brock GN, Pihur V, Pisano MM, Greene RM. TGFβ-1 and Wnt-3a interact to induce unique gene expression profiles in murine embryonic palate mesenchymal cells. Reproductive Toxicology (2010) in press.
- Jin JZ, Tan M, Warner DR, Darling DS, Higashi Y, Gridley T, Ding J. Mesenchymal cell remodeling during mouse secondary palate reorientation. Developmental Dynamics 239:2110-2117 (2010).
- Horn KH, Warner DR, Pisano M, Greene RM. PRDM16 expression in the developing mouse embryo. Acta Histochemica [Epub Oct 21] (2009).
- Warner DR, Smith HS, Webb CL, Greene RM, Pisano MM. Expression of Wnts in the developing murine secondary palate. International Journal of Developmental Biology. 53:1105-1112 (2009).