The Function Of Gpr177 During Tongue Development

The tongue is a complex muscular organ constituted by striated muscle,cranial neural crest cell(CNCC)-derived mesenchyme,and a stratified,squamous,non-keratinized epithelium.However,how the regulation of each tongue tissue is orchestrated in development remains to be explored.Wnt signaling pathway plays an important role in the tissue development and homeostasis.There are many Wnt ligands expressed on the tongue epidermis,however,the effect of these Wnt ligands on tongue development has not been studied.Gprl77 is a highly conserved Wnt signaling protein that regulates the transportation and secretion of Wnt ligands.Our previous study has shown that Gpr177 is expressed both epithelium and mesenchyme of mouse developing tongue,and that Shh-Cre mediated deletion of epithelial Gpr177 leads to inhibited lingual fungiform placode development.In addition,Gpr177 knockout leads to deformed tongue development,however,the intrinsic mechanism was not investigated because the previous study was focused on the development of the taste papillae,but not the developmental defects of the tongue and the causes of the tongue defects.In this study,we systematically study the effect of Gpr177-mediated Wnt signaling pathway on tongue development and the intrinsic regulatory mechanisms.We find that mutant mice exhibited tongue epithelium,lamina propria,and superior longitudinal muscle defects.We further find that decreased proliferation and differentiation of connective tissue and muscle cells leads to the tongue defects.In addition,down-regulation of Wnt signaling pathway lead to decreased Notch signaling activity,which affect the expression of downstream target gene Pax7,which play a critical role in promoting the proliferation of muscle precursor cells.Finally,we found that the Notch signaling pathway feedbacks to inhibit the activity of the Wnt signaling pathway during tongue development.In summary,we find that a Wnt/Notch/Pax7 cascade signal is involved through tissue interaction in tongue development,to regulate the development of tongue muscles.