Title: The Role of Sox2 as a Downstream Effector in ESRP1 -/- Induced Cleft Lip and Palate Formation in Mice
Lansara Jaruthien (Presenter)
University of Pennsylvania School of Dental Medicine
Guang Yan, Children's Hospital of Philadelphia
Russ Carsten, University of Pennsylvania School of Medicine
Hyun-Duck Nah, Children's Hospital of Philadelphia
Objectives: Although many genetic mutations have been associated with cleft lip and palate, there are still many gaps in our understanding of the genetic pathways that caused the defect during embryological development. Earlier studies have shown that knockout of ESRP1 (Epithelial Splicing Regulatory Protein 1) led to 100% penetrance of cleft lip and cleft palate in mice. ESRP1 regulates not only epithelial tissue specific alternative splicing but also epithelial gene expression, such as Sox2 gene, which determines proliferation and differentiation of oral epithelial cells. The object of the study was to determine and record the presence or absence of cleft lip and palate in ESRP1 knockout mice with Sox2 haploinsufficiency as compared to ESRP1 knockout mice.
Methods: ESRP1+/-:Sox2+/- and ESRP1+/-:Sox2 +/+ breeder mice was time-mated to produce E16.5 embryos. The embryos were harvested and photographed (Olympus MVX10). Tails were saved for genotyping of the embryos.
Results: There was a 100% rescued cleft lip rate in all 7 embryos with ESRP1-/-;Sox2+/- genotype combined from 5 litters. Adhesion of lateral nasal prominences to both maxillary and medial nasal prominences, as well as adhesion of medial nasal prominence to maxillary prominence were observed in 100% of the rescued samples. On the other hand, confluent fusion of lateral nasal prominence and maxillary prominent was only observed unilaterally in 1 sample, confluent fusion of lateral nasal prominence and medial nasal prominence was observed in 2 samples, and confluent fusion of medial nasal prominence and maxillary prominence was observed in 2 samples, with partial confluent fusion in 3 samples.
Conclusions: It was clear that all 7 embryos did not show identical rescued phenotype presentation but rather are rescued on a spectrum based of adhesion and confluence characteristics between different facial processes. Future studies are needed to understand interactive roles of ESRP1 and Sox2 in oral epithelial cell development in the developing face.