Disease relevance of ac

• Mutations in the suppressor of Hairy-wing [su(Hw)] gene of Drosophila melanogaster can cause female sterility and suppress mutations that are insertions of the gypsy retrotransposon [1].
• The gypsy insulator, a 350-bp element isolated from the Drosophila gypsy retrovirus, contains twelve degenerate binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein [2].
• The human homolog 1 of the Drosophila neurogenic achaete-scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines [3].

Psychiatry related information on ac

• Expression of achaete-scute at these two critical periods depends on cis-regulatory elements of the achaete-scute complex (AS-C) [4].

High impact information on ac

• The suppressor of Hairy wing (su(Hw)) protein inhibits the function of transcriptional enhancers located distally from the promoter with respect to the location of su(Hw)-binding sites [5].
• The development of most epidermal sensory organs in Drosophila is controlled by achaete and scute, two of the genes of the achaete-scute complex (AS-C) [6].
• Like the ASC products, ato protein contains a basic-helix-loop-helix region and heterodimerizes with daughterless protein to bind to E boxes [7].
• In the Drosophila peripheral nervous system, proneural genes of the achaete-scute complex (ASC) are required for formation of the precursors of external sense organs but not of chordotonal organs [7].
• The formation of a heterodimer between the daughterless and achaete-scute T3 products may explain the similar phenotypes of mutants at these two loci and the genetic interactions between them [8].

Biological context of ac

• These and other data suggest that the excess function phenotypes of Hw mutations are generated by an increase in achaete or scute transcripts [9].
• Molecular genetics of the achaete-scute gene complex of D. melanogaster [10].
• We show that the extreme Hw49c allele contains an inversion with a breakpoint within the AS-C, while the weak Hw685 allele is associated with a terminal deletion of the X chromosome which removes the achaete region of the AS-C [11].
• Nevertheless, the effects of ectopic AS-C gene expression show that T3 and T5 proteins display weak but significant feminizing activities, enhancing male-lethality, and rescuing the female-lethality of sis mutations [12].
• In the region upstream of the achaete gene of the AS-C, we have identified three 'E box' consensus sequences that are bound specifically in vitro by hetero-oligomeric complexes consisting of the da protein and an AS-C protein [13].

Anatomical context of ac

• Second, one cell of each cluster accumulates ac transcripts at a high level ('determined' stage) and becomes the neural progenitor cell [14].
• We have examined the pattern of expression of ac and its regulation during embryogenesis. ac is expressed at particular locations of the ectoderm according to a highly dynamic and complex pattern [14].
• A study of shaggy reveals spatial domains of expression of achaete-scute alleles on the thorax of Drosophila [15].
• We find that the peripheral nervous system of achaete null mutant larvae and imagos lacks any detectable phenotype [16].
• Here we study the expression of three of these genes (T3, T4, and T5) and show that their transcripts accumulate at the blastoderm stage in periodic patterns coincident with the dorsoventral extent of the neuroectoderm [17].

Associations of ac with chemical compounds

• A leucine zipper domain of the suppressor of Hairy-wing protein mediates its repressive effect on enhancer function [18].
• Two spontaneous mutations of rudimentary, the gene encoding the first steps of de novo pyrimidine biosynthesis in Drosophila, are suppressed by mutant alleles of the suppressor of Hairy-wing locus [19].

Physical interactions of ac

• In achaete-scute complex and daughterless mutants the interstitial cell precursors do not develop and the number of adult midgut precursors is strongly reduced [20].
• The activated NICD, interacting with Suppressor of Hairless [Su(H)], stimulates genes of the E(spl) complex, which in turn repress the proneural genes achaete/scute [21].

Regulatory relationships of ac

• Moreover, chn is activated by ac/sc in proneural clusters [22].
• First, vnd is required to activate proneural cluster formation within the medial column of every other neuroblast row through regulatory elements located 3' to ac; second, through a 5' regulatory region, vnd functions to increase or maintain proneural gene expression in the cell within the proneural cluster that normally becomes the neuroblast [23].
• u-shaped encodes a zinc finger protein that regulates the proneural genes achaete and scute during the formation of bristles in Drosophila [24].
• Activation of Notch leads to repression of the achaete-scute genes which themselves regulate transcription of Delta, perhaps directly [25].
• The development of external sensory organs on the notum of Drosophila is promoted by the proneural genes achaete and scute [26].

Other interactions of ac

• The yellow locus is the most distal and is followed, proximally, by the achaete and the scute loci [10].
• Spatial regulation of proneural gene activity: auto- and cross-activation of achaete is antagonized by extramacrochaetae [27].
• Two additional polyadenylated RNAs are transcribed from the achaete (1.1 kb) and yellow (1.9 kb) loci [10].
• Interactions between chip and the achaete/scute-daughterless heterodimers are required for pannier-driven proneural patterning [28].
• We also show that in Hw685 a moderate overexpression of the T4 gene largely replaces the absence of the T5 gene in the development of the notum chaetae pattern [11].

Analytical, diagnostic and therapeutic context of ac

• In situ hybridizations to Hw49c and Hw1 larval sections show that the overexpression causes an abnormally generalized distribution of T4 and/or T5 transcripts in imaginal discs [11].

References