Gas1 regulates embryonic tongue muscle proliferation, differentiation and maturation via alternative pathways to Hedgehog signaling.

Hedgehog (HH) signaling supports tongue and taste organ development. While the tongue is highly muscular, the role of HH signaling in muscle growth remains poorly understood. We recently showed the expression of HH receptor Gas1 in postnatal lingual muscle. To understand the role of Gas1 in the embryonic tongue, we first examined its expression using Gas1lacZ mouse and GAS1 immunostaining. Our results reveal parallel gene and protein expression in epithelial taste buds, stroma and muscles. We assessed Gas1 constitutive and muscle-specific conditional (E12.5-E18.5) gene deletion effects at E18.5. Constitutive Gas1 deletion disrupts myoblast count, cell proliferation, differentiation, maturation and motor structures, and differentially affects the size and number of intrinsic tongue muscles. We unmask the expression of other HH co-receptors, CDON and BOC, in lingual epithelium, stroma or muscles, which, along with HH-responding GLI1 cells, persists, despite Gas1 deletion. We propose an interplay of Gas1 in distinct lingual compartments for tongue myogenesis, which is independent of HH signaling. We also suggest that while the cell-intrinsic roles of Gas1 in muscle development may be redundant with other HH co-receptors, its cross-compartmental function is not.