PT  - JOURNAL ARTICLE
AU  - SungKyoung Lee
AU  - Matthew J. Sears
AU  - Zijun Zhang
AU  - Hong Li
AU  - Imad Salhab
AU  - Philippe Krebs
AU  - Yi Xing
AU  - Hyun-Duck Nah
AU  - Trevor Williams
AU  - Russ P. Carstens
TI  - Cleft lip and cleft palate (CL/P) in <em>Esrp1</em> KO mice is associated with alterations in Wnt signaling and epithelial-mesenchymal crosstalk
AID  - 10.1101/2019.12.12.874636
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 2019.12.12.874636
4099  - http://biorxiv.org/content/early/2019/12/12/2019.12.12.874636.short
4100  - http://biorxiv.org/content/early/2019/12/12/2019.12.12.874636.full
AB  - Cleft lip is one of the most highly prevalent birth defects in human patients. However, there remain a limited number of mouse models of cleft lip and thus much work is needed to further characterize genes and mechanisms that lead to this disorder. It is well established that crosstalk between epithelial and mesenchymal cells underlies formation of the face and palate, yet the basic molecular events mediating this crosstalk are still poorly understood. We previously demonstrated that mice with ablation of the epithelial-specific splicing factor Esrp1 have fully penetrant bilateral CL/P. In this study we further investigated the mechanisms by which ablation of Esrp1 leads to cleft lip as well as cleft palate. These studies included a detailed analysis of the changes in splicing and total gene expression in embryonic ectoderm during formation of the face as well as gene expression changes in adjacent mesenchyme. We identified altered expression in components of pathways previously implicated in cleft lip and/or palate, including numerous components of the Wnt signaling pathway. These findings illustrate that maintenance of an Esrp1 regulated epithelial splicing program is essential for face development through regulation of key signaling pathways.