Interaction Affecting Craniofacial Muscle Differentiatio

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DESCRIPTION (provided by applicant): Craniofacial muscles show great structural and functional diversity, and anomalies in their development contribute to a wide range of problems in vision, facial expression, mastication, and phonation. However, little is known about processes controlling the differentiation and maturation of branchial and extra-ocular muscles. Head muscles arise in mesenchyme adjacent to the brain then migrate and differentiate in connective tissues derived from the neural crest. Trunk and limb muscles arise in epithelial myotomes, then differentiate in paraxial and lateral mesoderm. This research will characterize tissue interactions necessary (1) to promote early differentiation of branchial and extra-ocular muscle myoblasts and (2) to direct expression of fiber typespecific myosins in primary myotubes in these muscles. These interactions will be identified by transplanting specific muscle precursors, at different stages and with or without putative muscle-inducing tissues, between head and trunk axial levels. Assays of tissue response include expression of myoblast markers (e.g., my, about, myoD), of trunk or head muscle-specific markers (e.g., parc aboutcis, pax3; podl, barx2, Ibxl,en2), and at later stages of muscle-specific myosin heavy chains. Surgeries are done on quail and chick embryos, which are ideally suited for in vivo tissue recombination experiments and for which detailed cellular and molecular biographies of head muscles are uniquely available. A third specific aim will characterize the processes by which craniofacial muscles change their attachments during later growth and maturation stages. EM studies reveal that primary myotubes undergo focal degeneration at their myotendinous tips and also at mid-myotube regions during embryonic days 12-15. I propose that these focal degenerations are essential for normal remodeling of head muscles, but nothing is known of the processes or provocations for these focal losses. Assays for elements of the pathways known to be active during programmed cell death of mononucleated cells will be applied to normal and function- or growth-arrested head muscles. Collectively, these experiments will provide the first insights into the signals necessary for initiation and diverse differentiations of craniofacial muscles and the mechanisms by which remodeling of these head muscles occurs.