Functional Analysis of a Genomic Regulatory Region in Tooth Development


The goal of this project is to better understand the genetic control of early vertebrate tooth development. Several cell-signaling pathways are known to be necessary for proper tooth formation, but the signals sufficient to induce de novo tooth development remain elusive. Employing a comparative phylogenetic approach, we seek to identify evolutionarily conserved genomic cis-regulatory sequences located in the vicinity of Dlx2, a gene expressed relatively early in vertebrate tooth development. We will then functionally test the ability of identified sequences to control gene expression during tooth development using transgenic reporter experiments in fish embryos. The identification of such elements will help us narrow down the list of candidate trans-acting genes near or at the top of the tooth initiation regulatory cascade. Finally, we will test the function of these candidate factors to induce tooth organogenesis in zebrafish embryos. The results from fish will likely be applicable to vertebrate tooth development in general and may facilitate future regenerative dental therapies in humans.

Recent Publications and Presentations

  • William R. Jackman, Shelby H. Davies*, David B. Lyons*, Caitlin K. Stauder*, Benjamin R. Denton-Schneider*, Andrea Jowdry, Sharon R. Aigler, Scott A. Vogel*, and David W. Stock. (2012) Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth. Evolution and Development. (accepted)
  • Pawat Seritrakul*, Eric Samarut, Tenzing TS Lama*, Yann Gibert, Vincent Laudet, and William R Jackman. (2012) Retinoic acid expands the evolutionarily reduced dentition of zebrafish. The FASEB Journal. (epub ahead of print) doi: 10.1096/fj.12-209304
  • William R. Jackman, James J. Yoo*, and David W. Stock. (2010). Hedgehog signaling is required at multiple stages of zebrafish tooth development. BMC Developmental Biology 10:119.
  • Yann Gibert, Laure Bernard, Melanie Debiais-Thibaud, Franck Bourrat, Jean-Stephane Joly, Karen Pottin, Axel Meyer, Sylvie Retaux, David W. Stock, William R. Jackman, Pawat Seritrakul*, Gerrit Begemann and Vincent Laudet. (2010). Formation of oral and pharyngeal dentition in teleosts depends on differential recruitment of retinoic acid signaling. The FASEB Journal 24, 3298-3309.
  • Hana Littleford*, Andrea Jowdry, and William Jackman. Functional characterization of a tooth enhancer. The 10th International Conference on Zebrafish Development and Genetics, Madison, WI, June 20-24, 2012; and NIH, NIGMS Fourth Biennial National IDeA Symposium of Biomedical Research Excellence (NISBRE), Washington, DC, June 25-27, 2012.
  • Pawat Seritrakul*, Andrea Jowdry, Tenzing Lama*, Calli Coffee* and William Jackman. Retinoic acid expands the evolutionarily reduced dentition of zebrafish. 4th Northeast Regional IDeA Meeting, Newport, RI, August 10-12, 2011.