Disease relevance of ato

• Math5, a mouse homolog of the Drosophila proneural bHLH transcription factor Atonal, is essential in the developing retina to establish retinal progenitor cell competence for a ganglion cell fate [1].

High impact information on ato

• These results imply that ey does not induce the entire eye morphogenetic program but rather modifies ato-dependent neuronal development [2].
• In D. melanogaster, a common proneural gene called atonal (ato) functions in the initial process of development of a number of segment-specific organs, including the compound eye, the auditory organ and the stretch receptor, suggesting that these organs share an evolutionary origin [2].
• Like the ASC products, ato protein contains a basic-helix-loop-helix region and heterodimerizes with daughterless protein to bind to E boxes [3].
• atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system [3].
• The establishment and subsequent patterning of Atonal expression requires activity of the signalling transmembrane receptor Notch [4].

Biological context of ato

• M8SD elicits neural hypoplasia in eye discs, elicits loss of phase-shifted Atonal-positive cells, i.e. the 'founding' R8 photoreceptors, and consequently leads to apoptosis [5].
• We used ro(Dom) as a sensitive genetic background in which to identify mutations that affect hh signal transduction or regulation of ato expression [6].
• The time required for N signaling to inhibit ato expression was at most 90 min, but changes in the Dl protein distribution in mutant genotypes arose more slowly [7].
• The proneural proteins Atonal and Scute regulate neural target genes through different E-box binding sites [8].
• First, tandem repeats of 20-bp sequences containing E(Ato) and E(Sc) sites are sufficient to confer Atonal- and Scute-specific expression patterns, respectively, on a reporter gene in vivo [8].

Anatomical context of ato

• Expression of tll is normally confined to the optic lobe primordium, whereas ato appears in a subset of Bolwig's organ cells that we call Bolwig's organ founders [9].
• Initiation of Drosophila peripheral nervous system (PNS) development requires the achaete-scute complex (AS-C) and the atonal (ato) genes [10].
• atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain [11].
• Sensory neurons of the Atonal lineage pioneer the formation of glomeruli within the adult Drosophila olfactory lobe [12].
• Previously, we showed that targeted deletion of the atonal (ato) homologue math5 blocked the differentiation of most retinal ganglion cells (RGCs), revealing an essential role for math5 in RGC differentiation [13].

Enzymatic interactions of ato

• R8s in turn appear to signal through Rhomboid and Vein to create a patterned array of 'proneural clusters' which contain high levels of phosphorylated ERKA and the bHLH protein Atonal [14].

Regulatory relationships of ato

• N and Dl were required to repress ato in the vicinity of R8 cells, whereas sca had effects over several cell diameters [15].

Other interactions of ato

• E(spl)D, an allele of m8, encodes a truncated protein known as M8*, which, unlike wild type M8, displays exacerbated antagonism of Atonal via direct protein-protein interactions [5].
• Neither Atonal expression nor Bolwig's organ formation occurred in the absence of hedgehog, eyes absent or sine oculis activity [16].
• Normal ato or da activity is required for maintenance of MAPK activation [17].
• The b domains of ato and sc differ in seven residues [18].
• This supports a model of inhibitory interactions between proneural genes, whereby ato-like genes (amos and ato) must suppress sensory bristle fate as well as promote alternative sense organ subtypes [19].

Analytical, diagnostic and therapeutic context of ato

• In parallel, microarray analysis of wild-type versus ectopic ey-expressing tissue, followed by microarray-based epistasis experiments in an atonal (ato) mutant background, identified 188 genes induced by ey [20].

References