The absence of MyoD in regenerating skeletal muscle affects the expression pattern of basement membrane, interstitial matrix and integrin molecules that is consistent with delayed myotube formation

Summary s a member of a skeletal muscle specific family of transcription factors which directs the events of myogenesis during development and regeneration. Muscle cells that lack MyoD show delayed fusion in vivo and in vitro and defects have been observed in vitro in the attachment of MyoD(-/-) myoblasts to complex substrates such as Matrigel. Since interactions with the extracellular matrix (ECM) are important during myoblast fusion (i. e. myotube formation), it was hypothesised that expression of ECM molecules or their receptors may be altered in MyoD(-/-) muscle. The production of basement membrane molecules such as collagen type IV and several laminins, the interstitial molecules fibronectin and tenascin-C, and the cell surface molecules integrin α5 and α6 were quantitated in vitro using ELISA on cultured cells from MyoD(-/-) and wild type mice. Differences were observed in the production of fibronectin, tenascin-C, collagen type IV, laminin-1 and integrin α5 between control and MyoD(-/-) myotubes in vitro. This corresponded with delayed fusion of myoblasts in MyoD(-/-) cultures. On the basis of these findings with respect to matrix expression in vitro, fluorescent immunohistochemistry was carried out on adult whole muscle autografts to examine whether the expression of these molecuies, as well as integrin α7, was altered in the complex in vivo environment. Some minor differences in expression patterns were observed in MyoD(-/-) as compared to normal BALB/c autografts. The overall expression of matrix components was consistent with the delayed onset of myotube formation. These resuits suggest that the delay in myotube formation in MyoD(-/-) muscle is not a direct result of altered ex-pression of the matrix molecules collagen type IV, laminins, fibronectin, tenascin-C, and integrins α5, α6 or α7.