SPECIFICATION OF MUSCLE PATTERN IN THE AMNIOTE LIMB

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The molecular mechanisms underlying the specification of muscle pattern and the relationship of muscle pattern specification to skeletal and tendon pattern specification in the developing amniote limb are largely unknown. Myogenic precursor cells migrate into the limb and eventually differentiate into slow and fast myofibers arranged into 45 anatomical muscles. [To delineate when and where myogenic cells are being patterned, the fate of clonally-related myogenic cells will be analyzed by labeling myogenic precursors with CHAPOL replication defective retrovirus library.] lmx1 and hox transcription factors appear to be critical for specifying dorsal-ventral, anterior-posterior, and proximal-distal limb muscle pattern. The role of these genes in patterning particular phases of muscle morphogenesis will be assessed by retroviral misexpression of lmx1 and hoxd-11 in spatially inappropriate locations and at different times in the developing chick limb. Quail-chick chimeras and retroviral, tissue-specific manipulations of gene expression will determine how lmx1 and hoxd-11, initially expressed in the limb bud mesoderm, transmit their patterning information to muscle and provide an important means of dissecting the relationship between muscle, tendon, and skeleton morphogenesis during limb development. [In addition, novel genes involved in muscle patterning are being sought via a screen of a chick limb library for genes encoding secreted proteins].