TGF-ALPHA, EGF, AND THEIR COGNATE EGF RECEPTOR ARE COEXPRESSED WITH DESMIN DURING EMBRYONIC, FETAL, AND NEONATAL MYOGENESIS IN MOUSE TONGUEDEVELOPMENT

The developing mouse tongue provides a model for discrete patterns of morphogenesis during short periods of embryonic development. Occipital somite-derived myogenic cells interact with cranial neural crest-deri ved ectomesenchymal cells to form the musculature of the tongue. The b iochemical signals that control close range autocrine and/or paracrine signaling processes required to establish the fast-twitch complex ton gue musculature are not known. The present study was designed to test the hypothesis that desmin, epidermal growth factor (EGF), and transfo rming growth factor-alpha (TGF alpha) and their cognate receptor, epid ermal growth factor receptor (EGFr), are co-expressed during tongue my ogenesis and define specific developmental stages of tongue muscle cel l differentiation. To test this hypothesis, we performed studies to an alyze the timing, position, and concentration of desmin, TGF alpha, EG F, and EGFr from embryonic day 9 (E9) through birth in Swiss Webster m ouse tongue development, Desmin, TGF alpha, EGF, and EGFr co-localized to cells of myogenic lineage in the four occipital somites and subseq uently in myoblasts and myotubes from E9 through E17. By newborn stage , desmin is localized to discrete regions in myofibers corresponding t o Z-line delimiting sarcomeres, and A-band within sarcomeres; immunost aining for desmin, TGF alpha, and EGF persisted in differentiated myot ubes and striated skeletal muscle, Desmin increased from 0.01% at E11 to 0.5% of the total protein by E17 and at birth. Concomitantly, the p atterns and increases in TGF alpha, EGF, and EGFr showed significant i ncreases during the same developmental period. The temporal and positi onal colocalization of TGF alpha, ECF, and EGFr support the hypothesis that autocrine and paracrine regulation of desmin by actions of growt h factor ligand and receptor defines critical stages of tongue myogene sis. (C) 1997 Wiley-Liss, Inc.