Mi-2, the central component of the nucleosome remodeling and histone deacetylation (NuRD) complex, is known as an SNF2-type ATP-dependent nucleosome remodeling factor. No morphological mutant phenotype of Drosophila Mi-2 (dMi-2) had been reported previously; however, we found that rare escapers develop into adult flies showing an extra bristle phenotype. The dMi-2 enhanced the phenotype of ac(Hw49c), which is a dominant gain-of-function allele of achaete (ac) and produces extra bristles. Consistent with these observations, the ac-expressing proneural clusters were expanded, and extra sensory organ precursors (SOP) were formed in the dMi-2 mutant wing discs. Immunostaining of polytene chromosomes showed that dMi-2 binds to the ac locus, and dMi-2 and acetylated hisotones distribute on polytene chromosomes in a mutually exclusive manner. The chromatin immunoprecipitation assay of the wing imaginal disc also demonstrated a binding of dMi-2 on the ac locus. These results suggest that the Drosophila Mi-2/NuRD complex functions in neuronal differentiation through the repression of proneural gene expression by chromatin remodeling and histone deacetylation.