Hedgehog Signaling in Tongue Muscle Development: A Comparative Perspective With Limb Myogenesis

The mammalian tongue is an intricate skeletal muscle organ. From its initial formation to maturation, tongue muscle development involves precisely coordinated processes during embryonic and fetal phases of myogenesis. Extensive research on the regulatory pathways involved in tongue epithelial taste organ development has shown that the Hedgehog (HH) signaling pathway is vital to the formation and epithelial patterning of the tongue and taste organs. Emerging evidence also points to its involvement in the initial formation and spatial patterning of the tongue muscle. HH signaling is a well-established regulator of skeletal muscle development, particularly in limb myogenesis. However, structural and functional differences between limb and tongue muscles, as well as variations in their HH signaling regions, prevent the direct application of findings from limb muscles to the tongue. Consequently, a comprehensive comparative analysis is essential to establish the conserved and divergent mechanisms by which HH signaling operates in these distinct muscle systems. A detailed mechanistic understanding of HH signaling during lingual muscle formation and maturation is vital for fully elucidating its role in tongue function. Further, lingual myogenesis studies pave the way for potential regenerative therapeutic strategies for congenital anomalies and acquired conditions affecting the tongue. Thus, understanding the regulatory mechanisms of tongue muscle development has both biological and clinical importance. This review explores the role of HH signaling throughout the key stages of embryonic tongue muscle development (including myoblast determination, proliferation, differentiation, patterning, and maturation) and compares its role in limb myogenesis.