MAMMALIAN ACHAETE-SCUTE HOMOLOG-1 IS REQUIRED FOR THE EARLY DEVELOPMENT OF OLFACTORY AND AUTONOMIC NEURONS

The mouse Mash-1 gene, like its Drosophila homologs of the achaete-scu te complex (AS-C), encodes a transcription factor expressed in neural precursors. We created a null allele of this gene by homologous recomb ination in embryonic stem cells. Mice homozygous for the mutation die at birth with apparent breathing and feeding defects. The brain and sp inal cord of the mutants appear normal, but their olfactory epithelium and sympathetic, parasympathetic, and enteric ganglia are severely af fected. In the olfactory epithelium, neuronal progenitors die at an ea rly stage, whereas the nonneuronal supporting cells are present. In sy mpathetic ganglia, the mutation arrests the development of neuronal pr ecursors, preventing the generation of sympathetic neurons, but does n ot affect glial precursor cells. These observations suggest that Mash- 1, like its Drosophila homologs of the AS-C, controls a basic operatio n in development of neuronal progenitors in distinct neural lineages.