Integrated analysis identifying long non-coding RNAs (lncRNAs) for competing endogenous RNAs (ceRNAs) network-regulated palatal shelf fusion in the development of mouse cleft palate

Cleft palate (CP) results from failure of embryonic palate shelf apposition and fusion at the midline during embryogenesis (1) and is considered to be caused by the individual and combined effects of genetic and environmental factors (2,3). Epithelial-mesenchymal transition (EMT) of the medial-edge epithelium/midline epithelial seam (MEE/MES) is a crucial process of palatal shelf fusion during palatogenesis (4,5). Thus, any imbalance in MEE/MES cell proliferation and apoptosis, or dysfunction of EMT, may lead to CP formation during palatal shelf fusion (6). In mice, the embryonic palatal shelf first grows vertically in the oral cavity from embryonic gestation day 12.5 (E12.5) to E14; then, at E14.5, the palatal shelves are elevated to the horizontal position and contact each other to complete initial palatal fusion (6). However, the detailed mechanisms regulating palatogenesis remain unclear. Although microRNAs (miRNAs) and/or long non-coding RNAs (lncRNAs) are increasingly being recognized as playing important roles in the development and pathogenesis of several diseases, the regulatory mechanisms by which miRNAs and/or lncRNAs directly or indirectly interact during palatal shelf fusion remain elusive