Neuronal type information encoded in the basic-helix-loop-helix domain of proneural genes.
The proneural genes encode basic-helix-loop-helix (bHLH) proteins and promote the formation of distinct types of sensory organs. In Drosophila, two sets of proneural genes, atonal (ato) and members of the achaete-scute complex (ASC), are required for the formation of chordotonal (ch) organs and external sensory (es) organs, respectively. We assayed the production of sensory organs in transgenic flies expressing chimeric genes of ato and scute (sc), a member of ASC, and found that the information that specifies ch organs resides in the bHLH domain of ato; chimeras containing the b domain of ato and the HLH domain of sc also induced ch organ formation, but to a lesser extent than those containing the bHLH domain of ato. The b domains of ato and sc differ in seven residues. Mutations of these seven residues in the b domain of ato suggest that most or perhaps all of these residues are required for induction of ch organs. None of these seven residues is predicted to contact DNA directly by computer simulation using the structure of the myogenic factor MyoD as a model, implying that interaction of ato with other cofactors is likely to be involved in neuronal type specification.
Chien
C T
CT
Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.
Hsiao
C D
CD
Jan
L Y
LY
Jan
Y N
YN
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins; D003198:Computer Simulation; D003433:Crosses, Genetic; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D005260:Female; D017344:Genes, Insect; D018257:Helix-Loop-Helix Motifs; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009928:Organ Specificity; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014921:Wings, Animal / Q000033:anatomy & histology
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors