LINEAGE RESTRICTION OF THE MYOGENIC CONVERSION FACTOR MYF-5 IN THE BRAIN

myf-5 is one of four transcription factors belonging to the MyoD famil y that play key roles in skeletal muscle determination and differentia tion. We have shown earlier by gene targeting nlacZ into the murine my f-5 locus that myf-5 expression in the developing mouse embryo is clos ely associated with the restriction of precursor muscle cells to the m yogenic lineage. We now identify unexpected expression of this myogeni c factor in subdomains of the brain. myf-5 expression begins to be det ected at embryonic day 8 (E8) in the mesencephalon and coincides with the appearance of the first differentiated neurons; expression in the secondary prosencephalon initiates at E10 and is confined to the ventr al domain of prosomere p4, later becoming restricted to the posterior hypothalamus. This expression is observed throughout embryogenesis. No other member of the MyoD family is detected in these regions, consist ent with the lack of myogenic conversion. Furthermore, embryonic stem cells expressing the myf-5/nlacZ allele yield both skeletal muscle and neuronal cells when differentiated in vitro. These observations raise questions about the role of myf-5 in neurogenesis as well as myogenes is, and introduce a new lineage marker for the developing brain.