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-scute complex (AS-C), encodes a transcription factor expressed in neural precursors. We created a null allele of this gene by homologous recombination in embryonic stem cells. Mice homozygous for the mutation die at birth with apparent breathing and feeding defects. The brain and spinal cord of the mutants appear normal, but their olfactory epithelium and sympathetic, parasympathetic, and enteric ganglia are severely affected. In the olfactory epithelium, neuronal progenitors die at an early stage, whereas the nonneuronal supporting cells are present. In sympathetic ganglia, the mutation arrests the development of neuronal precursors, preventing the generation of sympathetic neurons, but does not affect glial precursor cells. These observations suggest that Mash-1, like its Drosophila homologs of the AS-C, controls a basic operation in development of neuronal progenitors in distinct neural lineages.
Guillemot
F
F
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Lo
L C
LC
Johnson
J E
JE
Auerbach
A
A
Anderson
D J
DJ
Joyner
A L
AL
D000313:Adrenal Medulla / Q000294:innervation; D000818:Animals; D000831:Animals, Newborn; D001341:Autonomic Nervous System / Q000002:abnormalities / Q000196:embryology*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002838:Chromaffin System / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004848:Epithelium / Q000196:embryology; D005724:Ganglia / Q000002:abnormalities / Q000196:embryology; D005804:Genes, Lethal; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009432:Neural Crest / Q000196:embryology; D009457:Neuroglia; D009475:Neurons, Afferent; D009831:Olfactory Mucosa / Q000002:abnormalities / Q000196:embryology* / Q000294:innervation; D010641:Phenotype; D013234:Stem Cells; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse