Justin Hu
Pronouns: He/Him
Research Mentor(s): Vesa Kaartinen
Co-Presenter:
Research Mentor School/College/Department: BMS / Dentistry
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors: Justin Hu, Max Hu, Ghazi Saroya, Chris Panaretos, Vesa Kaartinen
Presenter: 68
Abstract
Cleft palate, one of the most common birth defects among children, is the failed fusion of the palatal shelves during embryonic development. Prior research has found that periderm cells on the medial edge of each shelf of the secondary palate are crucial to preventing premature adhesion, yet a previous lack of effective genetic tools has made characterization of periderm cell fate in palatogenesis difficult. This current study has identified cytokeratin-6a (K6a) to be specific to periderm cells, enabling the development of the novel K6aiCre and the tamoxifen-inducible K6aiCreERT2 driver lines with CRISPR-Cas9 gene editing technology at the K6a locus in mice. These mice were crossed with general reporter Rosa26-mTmG mice to identify the cellular fate of the periderm. We found that rather than just slough off, migrate, or undergo apoptosis as previous studies have suggested, at the point of shelf contact, the periderm cells differentiate from a squamous to more cuboidal shape, resembling that of basal epithelial cells, which is associated with a loss of protective function. Additionally, the importance of Transcription Growth Factor-ß (TGF-ß) signaling in palatogenesis regulation was identified by knocking out TGF-ß Type 1 receptor (Alk5) in periderm cells, causing a high proportion of cleft phenotypes in the secondary palate. In the subsequent lineage-tracing, we observed a lack of periderm cell differentiation resulting in failure of palatal shelf fusion. The future of this study will see usage of single-cell RNA sequencing to identify the specific role of the TGF-ß signaling pathway in periderm cell differentiation. This study’s development of the K6aiCre driver line and the valuable information regarding periderm cell fate gleaned from using the driver line creates potential opportunities to generate future therapeutic treatments for cleft palate.
Biomedical Sciences, Interdisciplinary
