The National Institutes of Health and The National Institute of Dental and Craniofacial Research awarded Huojun Cao, associate professor in the Iowa Institute for Oral Health Research, and Eric Van Otterloo, assistant professor in the Iowa Institute for Oral Health Research, a five-year $2.2M+ grant for their project, Identifying the core transcriptional regulatory network initiating a tooth program.

The dental lamina is a thin epithelial band that forms on the oral epithelium of a developing embryo. The dental lamina is responsible for the development of teeth, yet little is known about what genetic regulatory networks govern this process.

One way that scientists identify how this process works is by knocking out various transcription factors that may regulate this process. Knocking out a gene allows the researchers to see what the outcomes would be if a subject lacked a single transcription factor, or a group of transcription factors. By observing the outcomes, the researchers gain greater understanding of how teeth develop.

Some transcription factors appear to govern which part of the teeth the cells develop into (specification), and other transcription factors appears to govern the healthy development of teeth.

Among these transcription factors, Cao and Van Otterloo have noted an interesting phenomenon. Knocking out a single transcription factor from among those that regulate these processes did not detrimentally affect tooth development. But, when two or more are knocked out, teeth did not develop normally. This, Cao and Van Otterloo argue, suggests that this regulatory process is governed by a redundant network of transcription factors. Knocking out one such transcription factors would not impact tooth development, but two or more of certain ones would impact tooth development. 

This grant provides resources for Cao and Van Otterloo to determine the precise relationships between the transcription factors involved, exploring genetic redundancies and how they govern the processes of tooth development. This will allow them to identify and determine the smallest group of transcription factors that are jointly sufficient to drive tooth developmental processes. 

The resulting advances in the science of tooth development could lay the foundation for applications intended to repair or regeneration teeth for children or adults.

Cao and Van Otterloo’s research team also includes Shankar Rengasamy Venugopalan, adjunct professor in orthodontics, and Colin Kenny, research assistant professor of surgery.

Research reported on this website was supported by the National Institutes of Health and the National Institutes of Dental and Craniofacial Research under Award Number 1R01DE033009-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.