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Investigator
Regenerative Biology
Environmental Stress Biology
Ph.D., Vanderbilt University, Biophysics, 1995
B.Sc., Texas A&M, Molecular Biology, 1989
The research interests of my laboratory focus on understanding the molecular mechanisms underpinning development of the lower jaw and how they are affected by their interaction with the environment. The bulk of our work is carried out using zebrafish (Danio rerio) because of its genetic tractability, its defined genome, and its evolutionary conservation with other vertebrates, including humans. The tools used in our laboratory include gene function knockdown by morpholino techniques; epifluorescence and confocal microscopy; histology; toxicogenomics, proteomics, and transcriptomics; and basic molecular biology techniques.
Recent work in my laboratory has shown that dioxin-activated aryl hydrocarbon receptor (Ahr) induces transcription of the forkhead box transcription factor, FoxQ1b, in the jaw primordium of zebrafish. Ongoing studies focus on defining the pathways regulated by FoxQ1b in order to understand how perturbation of FoxQ1b levels results in jaw abnormalities. We are also investigating other targets of Ahr regulation with critical roles in vertebrate development.
Our research is funded by the NIEHS (5R21 ES017828), and the Cleft Palate Foundation.
Understanding Vertebrate Jaw Development
Craniofacial development begins with the migration of cranial neural crest cells, a multipotent population of cells, from the dorsal embryonic brain into the branchial arches located in the anteroventral region of the embryo. The anterior-most branchial arch, BA1, is subdivided into two functionally distinct regions: the upper, or dorsal, region gives rise to the maxilla and the lower, or ventral, region gives rise to the mandible. My laboratory recently demonstrated that misregulating specific members of the forkhead box family of transcription factors, either by environment or mutation, leads to a severely compromised lower jaw, or mandible. However, we do not know what the targets of transcriptional regulation by these forkhead box proteins are.
The zebrafish, Danio rerio, is an ideal model in which to study the pathways leading to jaw development. It is a vertebrate and thus evolutionarily related to humans, it is genetically tractable and it is easily manipulated by techniques designed to affect gene function, and its jaw development is thought to be regulated by the same signaling pathways that regulate jaw development in humans. Currently, we have a number of projects in the lab that address the role of forkhead box proteins in jaw development. Opportunities for students to study embryonic development are available and use a number of cutting-edge techniques, including gene knock-down, chromatin immunoprecipitation, proteomics, microscopy, bioinformatics and genomics, as well as more conventional molecular biological techniques.
Carolyn Mattingly, PhD Co-Investigator
Michael Jose, Research Assistant