Dr. Huojun Cao, associate professor in the Department of Endodontics, and Dr. Eric Van Otterloo, associate professor in the Department of Periodontics, have received a five-year, $3+ million R01 grant from the National Institute of Dental and Craniofacial Research (NIDCR) to investigate how genetic networks guide the development of oral, dental, and skin tissues in the areas around the mouth.
The project, Identifying transcriptional interplay between skin and oral ectoderm during mandibular patterning, focuses on understanding how specific groups of transcription factors interact to determine whether cells in the embryonic jaw become oral tissue, teeth, or skin. Transcription factors are proteins that regulate gene expression. These developmental steps are critical, as disruptions in these processes can lead to congenital defects such as cleft lip, malformed teeth, or other craniofacial anomalies.
Rather than examining each transcription factor in isolation, the research will explore how two key sets of transcription factors (SOX2/PITX1/PITX2 and TFAP2A/TFAP2B) work together or in opposition to shape the early embryonic ectoderm into distinct tissue types. The team will use genomic tools and gene knockouts to study how these factors influence both the surface tissues of the face and the underlying mesenchyme, which contributes to tooth formation. 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.
The grant aims to uncover how TFAP2 factors suppress oral and dental development to promote skin development, how they modify chromatin in skin development, and how changes in epithelial patterning affect the deeper tissues that give rise to teeth. Together, these investigations will provide a more complete picture of how facial tissues are specified during development.
This research builds on previous collaborative work between Dr. Van Otterloo and Dr. Cao, including studies on transcriptional regulation in tooth development and craniofacial patterning. Their combined expertise in developmental biology, genomics, and bioinformatics positions them to make significant contributions to the field.
Ultimately, the project aims to uncover mechanisms that could inform regenerative therapies for dental and skin tissues and improve understanding of genetic syndromes that affect craniofacial development. The research may also provide insights into how to reprogram cells for tissue repair, offering hope for future clinical applications.
Dr. Colin Kenny, assistant professor in the Department of Surgical Oncology and Endocrine Surgery, is a co-investigator on the project.
Research reported on this website is being supported by the NIDCR under Award Number 1R01DE034668-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.