Specification of the Drosophila CNS midline cell lineage: direct control of single-minded transcription by dorsal/ventral patterning genes.

The Drosophila CNS consists of a bilaterally symmetric group of neurons separated by a discrete group of CNS midline cells. The specification of the CNS midline cell lineage requires transcription of the single-minded gene. Genetic evidence suggests that a group of transcription factors, including Dorsal, Snail, Twist, and Daughterless:: Scute, is required for initial single-minded transcription. Comparison of the DNA sequences of the single-minded gene regulatory regions between two Drosophila species reveals conserved sequence elements. Biochemical studies using purified proteins indicate that a number of these conserved sequences represent binding sites for Dorsal, Snail, and Twist. In vitro mutagenesis combined with germline transformation indicates that these binding sites are required in vivo for single-minded mesectodermal transcription. These results show that single-minded transcription and, thus, CNS midline specification is directly controlled by dorsal/ventral patterning transcription factors. They also suggest a model in which multiple transcriptional activators function in a cooperative, concentration-dependent mode in combination with a transcriptional repressor to restrict single-minded transcription to the CNS midline precursor cells.