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NIH grant 1F31DE036431-01: Tissue patterning and partitioning across the oral-aboral axis during mouse mandibular development
Institute: {'code': 'DE', 'abbreviation': 'NIDCR', 'name': 'National Institute of Dental and Craniofacial Research', 'admin_org_id': '12500070', 'admin_funding_url': ''}. PI: Jaclyn Olberding. Award: $47617.
Start: 2026-09-30T00:00:00.
PROJECT SUMMARY
Craniofacial anomalies are the 2nd leading structural malformation to appear at birth; however, our limited
understanding of the molecular mechanisms controlling craniofacial development has prevented us from
developing strategies for effective treatment and prevention. The long-term goal of this study is to advance our
knowledge of mandibular associated malformations and regenerative strategies of epithelial lineages, including
oral mucosa, teeth, and skin. Our lab, among others, has identified that transcription factor and signaling pathway
groups SOX2/SHH and TFAP2/WNT pattern the oral-aboral axis, respectively, of the mandibular epithelium.
Emphasis in previous studies has focused on how mesenchymal signals contribute to mandible development,
while the roles of epithelial inductive signals remain undefined. Thus, the overall objective of the proposed study
is to determine how interactions between oral and aboral epithelial transcription factors drive the specification of
oral/dental or skin fates in the mandible. To approach this objective, we will test the central hypothesis that during
mandibular development, epithelial gene programs across the oral-aboral axis repress and antagonize each
other, while directly autoregulating themselves, to give rise to the oral mucosa and the aboral skin. In AIM 1 we
will employ genome-wide, epigenome-wide (CUT&RUN, ATAC-seq), and biochemical assays (Co-IP,
Luciferase) to decipher if and how SOX2 and TFAP2 transcription factors repress each other across the oral-
aboral axis at the DNA and protein level. In AIM 2 we will couple mouse genetics and ex vivo whole embryo
roller bottle culture to evaluate how SHH and WNT pathways downstream of SOX2 and TFAP2, respectively,
aid in regulating the epithelial partitioning of the oral-aboral axis. Completion of these aims will fill a critical gap
in our knowledge of how the epithelial layer guides development of the mandible. Such knowledge will contribute
to the development of regenerative strategies of an oral or skin lineage or may even prevent disorders that span
this axis. The applicant, Jaclyn (Jackie) Olberding, has a diversified training in mouse genetics, embryology, and
other fundamental molecular techniques described in this proposal. Under the mentorship of Dr. Eric Van
Otterloo, the applicant will deepen her research training by developing skills in genome-wide molecular assays,
next generation sequencing approaches, bioinformatic techniques, biochemical assays, and ex vivo
methodologies. The training plan, established team, and institutional environment outlined in this research
proposal will not only pave the way to improving craniofacial treatment and health, but also support her in her
career goal of becoming a rigorous independent researcher.document fetched 2026-10-15 02:48