David Clouthier, Ph.D.
Associate Professor
Craniofacial Biology
Ph.D., University of Texas Southwestern Medical Center at Dallas, 1994
Genetics of craniofacial and cardiovascular development
Research Interests
My lab is focused on elucidating the molecular signals involved in neural crest cell (NCC) patterning during craniofacial and cardiovascular development. NCCs originate along the dorsal lip of the neural tube, migrating away around the time of tube closure to the pharyngeal arches and arch arteries. Once there, they form the bone, cartilage and connective tissue of the face and neck and the smooth muscle surrounding the great vessels. In addition, they contribute to septal and valve formation in the heart. Many signals contribute to NCC patterning, with these signals organized into hierarchical pathways. One or more of these pathways is regulated by endothelin-A (Ednra) receptor signaling. We have recently shown that targeted inactivation of the Ednra gene in mice leads to loss of identity in specific NCCs and subsequent homeotic transformation of lower jaw structures into upper jaw-like structures. Ednra mutant embryos die shortly after birth from these defects. By elucidating the molecular signals that are normally induced by Ednra signaling and subsequently drive NCC patterning, we hope to better understand how perturbation of these signals results in facial and heart birth defects. Since birth defect syndromes affecting the face and heart account for the majority of human birth defects observed, we expect our findings will be of significant interest to both basic and clinical scientists.
Biography
Publications
Clouthier, D.E., Williams, S.C., Richardson, J.A., Yanagisawa, H., Hammer, R.E. and Yanagisawa, M. (2000). Signaling pathways crucial for craniofacial development revealed by endothelin-A receptor-deficient mice. Dev. Biol. 217:10-24.
Yanagisawa, H., Hammer, R. E., Richardson, J. A., Emoto, N., Williams, S. C., Takeda, S., Clouthier, D. E. and Yanagisawa, M. (2000). Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development. J. Clin. Invest. 105:1373-1382.
Charité, J., McFadden, D.G., Merlo, G., Levi, G., Clouthier, D.E., Yanagisawa, M., Richardson, J.A., and Olson E.N. (2001). Endothelin-1 signaling to a dHAND branchial arch enhancer is mediated by Dlx6. Genes Dev. 15: 3039-3049
Yanagisawa, H., Clouthier, D.E., Richardson, J.A., Charite, J. and
Olson, E.N. (2003). Targeted deletion of a branchial arch-specific enhancer
reveals a role of dHAND in craniofacial development. Development 130:1069-1078.
Ruest, L.-B., Dager, M., Yanagisawa, H., Charité, J., Hammer,
R.E.,
Olson, E.N., Yanagisawa, M. and Clouthier, D.E. (2003). dHAND-Cre transgenic
mice reveal specific potential functions of dHAND during craniofacial
development. Dev. Biol. 257:263-277.
Clouthier, D.E., Williams, S.C., Hammer, R., Richardson, J.A. and Yanagisawa,
M. (2003). Cell-autonomous and non-autonomous actions of endothelin-A
receptor signaling in craniofacial and
cardiovascular development. Dev. Biol. 261:506-519.
Comerford, S.A., Clouthier, D.E., Hinnant, E.A. and Hammer, R.E. (2003) Induction of hepatocyte proliferation and death by modulation of T-antigen expression. Oncogene 22:2515-2530.
Ruest, L.-B., Hammer, R.E., Yanagisawa, M. and Clouthier, D.E. (2003). Dlx5/6-enhancer directed expression of Cre recombinase in the pharyngeal arches and brain. genesis, 37, 188-194.
Clouthier, D.E. and Schilling, T.F. (2004). Understanding endothelin-1 function during craniofacial development in the mouse and zebrafish. Birth Defects Res. Part C, Embryo Today 72:190-199.
Ruest. L.-B., Xiang, X., Lim, K.-L., Levi, G. and Clouthier, D.E. (2004). Endothelin-A receptor-dependent and independent signaling pathways in establishing mandibular identity. Development 131:4413-4423.
Maurer, M., Wedemeyer, J., Metz, M., Pillponsky, A.M., Weller, K., Chatterjea, D., Clouthier, D.E., Yanagisawa, M. M., Tsai, M. and Galli, S.J. (2004). Mast cells promote homeostasis by limiting endothelin-1-induced toxicity. Nature 432:512-516.
Ruest, L.-B., Kedzierski, R., Yanagisawa, M. and Clouthier, D.E. (2005) Deletion of the endothelin-A receptor gene within the developing mandible. Cell Tissue Res. 319:447-453.
Kanzaki-Kato, N., Tamakoshi, T., Fu, Y., Chandra, A., Itakura, T., Uezato, T., Tanaka, T., Clouthier, D., Sugiyama, T., Yanagisawa, M. et al. (2005). Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis. Cardiovasc. Res. 65, 711-718.
