The Drosophila single-minded gene is expressed in the embryonic central nervous system midline cells and plays a critical role in central nervous system development. Additional expression of single-minded is found in a subset of ventral muscle precursor cells. Null mutations of single-minded result in an alteration of the ventral oblique muscles, such that muscle fibers form inside the embryo above the central nervous system. This defect is due to the mislocalization of a subset of mesodermal precursor cells. The muscle defect observed in single-minded null mutations is not due to the absence of single-minded expression in muscle precursor cells and likely results from an influence of the central nervous system on ventral muscle development.

1. The midline cells of the Drosophila embryonic CNS comprise a discrete neuroanatomical structure consisting of a small subset of neurons and glia. 2. Developmental commitment of the CNS midline cells requires the action of dorsal/ventral patterning genes. 3. The single-minded gene encodes a basic-helix-loop-helix transcription factor and acts as a master regulator for the CNS midline lineage. 4. A number of different transcription factors and proteins involved in cell-cell interactions are necessary for the differentiation of midline neurons and glia. 5. CNS midline cells have important functions in the formation of the ventral epidermis and axon commissures.

Development of the Drosophila CNS midline cells is dependent upon the function of the single-minded (sim) gene. Sequence analysis shows that sim is a member of the basic-helix-loop-helix class of transcription factors. Cell fate experiments establish that sim is required for early events in midline cell development, including a synchronized cell division, proper formation of nerve cell precursors, and positive autoregulation of its midline expression. Induction of ectopic sim protein under the control of the hsp70 promoter shows that sim can direct cells of the lateral CNS to exhibit midline cell morphology and patterns of gene expression. We propose that sim functions as a master developmental regulator of the CNS midline lineage.