InteractiveFly: GeneBrief
poils au dos: Biological Overview | Regulation | Developmental Biology | Effects of Mutation |References
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Gene name - poils au dos
Synonyms - CG10309 Cytological map position - 89B13 Function - transcription factor |
Symbol - pad
FlyBase ID: FBgn0038418 Genetic map position - 3R Classification - C2H2 zinc fingers and N-terminal zinc-finger-associated domain (ZAD) Cellular location - nuclear |
Traditional screens aiming at identifying genes regulating development have relied on mutagenesis. A new gene has been identified involved in bristle development, identified through the use of natural variation and selection. Drosophila melanogaster bears a pattern of 11 macrochaetes per heminotum. From a population initially sampled in Marrakech, a strain was selected for an increased number of thoracic macrochaetes. Using recombination and single nucleotide polymorphisms, the factor responsible was mapped to a single locus on the third chromosome, poils au dos (French for 'hairy back'), that encodes a zinc-finger-ZAD protein. The original, as well as new, presumed null alleles of poils au dos are associated with ectopic achaete-scute expression that results in the additional bristles. This suggests a possible role for Poils au dos as a repressor of achaete and scute. Ectopic expression appears to be independent of the activity of known cis-regulatory enhancer sequences at the achaete–scute complex that mediate activation at specific sites on the notum. The target sequences for Poils au dos activity were mapped to a 14 kb region around scute. In addition, pad has been shown to interact synergistically with the repressor hairy and with Dpp signaling in posterior and anterior regions of the notum, respectively (Gibert, 2005).
The large bristles (macrochaetes) on the notum of fruit flies are arranged in a stereotyped array. Development of these bristles has been the focus of detailed genetic analysis. Bristle development is dependent on the activity of basic Helix-Loop-Helix transcription factors encoded by the achaete (ac) and scute (sc) genes. The positioning of bristles is achieved through precise spatial regulation of ac-sc expression in small clusters of cells, the proneural clusters, at the sites of the future bristles in third larval instar wing imaginal discs. Expression in proneural clusters is regulated by multiple, independently-acting cis-regulatory enhancer modules scattered throughout the 100 kb or so of the ac-sc complex (AS-C). These mediate activation by transcription factors such as Pannier and Araucan/Caupolican. Expression of ac-sc is then progressively refined within each cluster to the bristle precursors by autoregulation and Notch-mediated lateral inhibition. The bristle pattern also relies on the activity of repressors such as Hairy and Extramacrochaetae, which prevent accumulation of Ac-Sc at positions where proneural clusters do not form (Gibert, 2005 and references therein).
The pattern of bristles on the notum varies between Dipteran species and a few differences are even found within the genus Drosophila. Differences in the arrangements of bristles between species correlate with changes in the temporal-spatial expression patterns of ac-sc and at least one of their upstream regulators, pannier. So there must exist sufficient variation in the genes regulating bristle patterning within a species (Skaer, 2000) to serve as a substrate for the evolution of bristle patterning between species (Gibert, 2005).
Variation of bristle number in Drosophila has been a classical model for quantitative genetics. Quantitative trait locus (QTL) analysis of lines selected for an increased number of bristles, has shown that a small number of factors of large effect are usually involved. They often map close to genes with a known role in bristle development or more generally in nervous system development. Naturally occurring variation at some of these loci such as the AS-C, scabrous, the Delta-Hairless region, contribute to quantitative variation in bristle number. Most quantitative genetic studies have focussed on the sternopleural and abdominal bristles, which are highly variable compared to the bristles found on the notum. Indeed, a 'wild-type' pattern of 11 macrochaetes per heminotum is assumed to be fixed in D. melanogaster. However, natural variants of this pattern can be found and enough genetic variation exists in nature to select flies for an increased number of notal bristles. Selection experiments for ectopic dorso-central bristles have uncovered the influence of the genetic background and shown that the anterior and posterior dorso-central bristles can to some extent respond independently to selection (Gibert, 2005 and references therein).
In some cases, QTLs do not map close to genes known for their role in bristle development. The study of natural variants can therefore lead to the discovery of new genes and give insights into bristle patterning mechanisms. This study presents the analysis of a natural variant for the thoracic bristle pattern from a selected population of D. melanogaster initially sampled in Marrakech, Morocco, and uncovers a new gene involved in the regulation of ac-sc (Gibert, 2005).
An important question in evolutionary biology is to understand the relationship between intraspecific variability in morphological traits and their interspecific divergence. Selection experiments can help to answer this question, since they allow identification of the genetic variation relevant to a specific trait present in the selected population. In this study, the quick response to artificial selection has relied on the fixation of a single loss of function allele with a strong phenotypic effect. Interestingly, other examples from natural populations have shown that some important morphological variations, such as pelvic reduction in fresh-water sticklebacks can be caused by a major or even a single locus (Shapiro, 2004). However, previous studies on bristle QTL in selected lines of Drosophila have always identified several major QTLs. In the case of the DC bristles, the three major chromosomes contributed to the response to artificial selection in a previous experiment (Dominguez, 1993). It is therefore unusual that the phenotype in the selected line relies on a single bristle QTL (other loci may contribute quantitatively, but the pad1 mutation is necessary and sufficient for the phenotype). The pad1 mutation is probably present at very low frequency in Marrakech, since a second sample of flies collected in the same location did not give a strong response to selection, suggesting an absence of the mutation. Furthermore, the phenotype appears to be due to a single deleterious lesion in the pad gene; many single QTLs contain multiple mutations. It is not known whether deleterious variants of this kind contribute to long term evolution but such polymorphisms need not necessarily be devoid of evolutionary advantage. Indeed, some natural situations have been described where loss of function mutations presenting a particular advantage are rapidly fixed during an adaptative radiation. Recent examples in multicellular eukaryotes include loss of function mutations in a pigmentation gene inducing a shift of pollinators in Petunia (Gibert, 2005 and references therein).
The gene uncovered encodes a zinc-finger transcription factor with a ZAD domain. ZAD domains have only been described in insects where they are highly represented: there are about 80 of them in the Drosophila genome (Chung, 2002). Almost all are found in association with zinc finger domains. Few have been studied, but in several cases, point mutations in the ZAD domain have been shown to completely disrupt the function of the gene (Crozatier, 1992; Gaszner, 1999). The ZAD domain of the Grauzone transcription factor has recently been crystallized and shown to be a dimerization domain (Jauch, 2003). The global structure of the ZAD domains is remarkably conserved and so it is possible that different transcription factors are able to form heterodimers through their ZAD domains. The ZAD domain encoded in pad might therefore have a crucial role in establishing molecular interactions between different transcription factors (Gibert, 2005).
In addition to the bristle phenotype, the alleles pad2, pad3, and pad4 die as late pupae with twisted legs, a phenotype caused by abnormal eversion of leg imaginal discs during pupal development. Unlike these alleles which are predicted not to encode any protein, pad1 with a predicted truncated protein does not display this phenotype. A similar phenotype is seen in mutants of the gene crooked-legs which encodes a zinc-finger transcription factor showing significant similarity to Pad in the zinc fingers. It is the most closely related gene to pad in the D. melanogaster genome according to Blast analysis (Gibert, 2005).
pad is involved in the regulation of ac-sc. In pad mutants, expression of ac and sc is increased. The increase appears to be general in that the proneural clusters are enlarged, but in addition, other cells with high levels of Ac-Sc are seen in regions where these products are normally absent or barely detectable. This phenotype is reminiscent of the Hw mutations that are associated with a generalized increase in the levels of Ac and Sc (Balcells, 1988). Enlargement of the proneural clusters need not necessarily result from increased activity of the cis-regulatory sequences that normally drive them but can be seen as a consequence of a ubiquitous increase in gene expression. Indeed, these results suggest that ectopic bristles do not arise from proneural clusters. Use of the DC enhancer with a lacZ reporter shows that the ectopic bristles are outside the area of activity of this enhancer. Furthermore, DC bristles also form in the absence of this regulatory sequence [In(1)ac3 and Df(1)91B]. In wild-type flies, the precursors for the pDC and then later the aDC arise from the DC cluster. In pad mutants, a bristle immediately anterior to the pDC, the 'aDC', is outside the area of lacZ staining. This suggests that a bristle at this position, forms earlier in pad mutants from cells with a high level of ac-sc expression not driven by the endogenous enhancer. The presence of such a bristle would then prevent the formation of a precursor from the DC-driven cluster itself, by means of Notch-mediated inhibition. Scutellar bristles can also form in the absence of the scutellar enhancer [In(1)sc4] and a reporter construct for the L3-TSM enhancer is unchanged in pad1. Therefore, pad is unlikely to act via each of the enhancer modules that mediate activation in proneural clusters. It is more probable that Pad acts as a repressor to prevent generalized accumulation of Ac-Sc over the notum and in particular outside the sites of the proneural clusters. The strong genetic interaction between pad and hairy, a known transcriptional repressor of ac-sc, as well as the synergism with Dpp signaling is in agreement with this hypothesis (Gibert, 2005).
This study identifed a 13 kb region around sc that is likely to contain sequences necessary for the formation of all ectopic bristles in pad mutants. It is hypothesized that these sequences direct a weak expression of ac-sc over the entire notum that is up-regulated in pad mutants. One possibility is that Pad acts on the sc promoter. Within the region delimited above, a 3.7 kb stretch upstream of the scute ATG, containing both the SOP enhancer and an enhancer for the wing L3-TSM region, is expressed in several proneural clusters and some other regions. In the absence of Ac and Sc, expression, albeit weak, of a 3.7 kb-lacZ reporter construct can still be detected in the regions of the DC and PSA bristles. Therefore, this fragment drives expression of sc prior to the onset of autoregulation. pad may act, directly or indirectly, via these sequences, allowing a level of Sc high enough in some cells for autoamplification and the adoption of a neural fate. This is visible in cells where the EE4-lacZ is activated, prior to expression of sens and activation of the SOP enhancer. Further studies are required to determine the mechanism of Pad function and whether these sequences are indeed a target for Pad (Gibert, 2005).
Variation of bristle number in Drosophila has been a classical model for quantitative genetics. Traditionally, the phenotype of interest is generated by selection followed by a search for the genetic factors responsible. Several QTLs causing variation in bristle number have been identified in this fashion (Gurganus, 1998; Long, 1995). However, their resolution at the single gene level has only been successful when candidate genes known to affect bristle development were found to map within the QTLs, as confirmed by the more detailed study of some of them. This is also true for studies on other models. In fact, there are very few examples where a new, previously unknown gene, has been shown to be responsible for a QTL. This can be attributed to the difficulty of obtaining enough informative recombinants within the QTL. Indeed, one of the rare successful examples corresponds to a QTL located in a recombination hot spot (Fridman, 2000). Furthermore, most quantitative traits are influenced by several QTL, which makes the mapping more difficult than in this study. The intensive focus on D. melanogaster as a genetic model has led to the development of a number of tools that allow the efficient mapping of mutations and the rapid, precise resolution of QTLs. The genome sequence now provides access to all genes and allows the sites of recombination to be mapped using SNPs. Furthermore, the generation of thousands of precisely located transposon insertions labeled with convenient markers such as white+, means that informative recombinants can be efficiently identified. Indeed, the use of Pw+ insertions located at proximity to the QTL significantly reduces the effort involved in SNP mapping, and also the cost, since the proportion of uninformative recombinants is much lower. In addition to quantitative variation of bristles, morphometric traits such as body weight, wing and thorax length, ovariole number or pigmentation, vary significantly between wild populations which have adapted locally (Gibert, 2004). These too could be amenable to studies allowing the identification of new regulatory genes. An advantage of natural variants is that the mutations responsible for phenotypic differences are likely to be less severe in general than the complete loss of function mutations frequently generated by traditional mutagenesis. Such hypomorphic mutations facilitate the study of adult phenotypes. Therefore, the combined use of natural variation observed in lines selected from wild populations of Drosophila and the powerful genetic tools provided by laboratory strains permits identification of new genes as illustrated here (Gibert, 2005).
Expression of ac-sc in proneural clusters is regulated by independently-acting cis-regulatory enhancers. The enhancer responsible for activation of ac-sc in the cluster giving rise to the DC bristles has been characterized in detail. The activity of this enhancer in a reporter construct was examined using lacZ expression. The activity of this enhancer is modified in pad1. The domain of expression of lacZ appears wider. At the same time, the anterior limit of the cluster is retracted in a posterior direction. It is possible that this is in part due to the slight distortion of the overall shape of the notum seen in pad1 mutants. Interestingly, the ectopic bristles do not arise within the misshapen proneural cluster. They are therefore formed independently of the activity of the DC enhancer used for activation. In fact, the aDC, as well as the ectopic DC precursors, are both clearly situated outside the DC cluster. Another characterized enhancer of ac-sc, the L3-TSM enhancer involved in the formation of the sensilla on the anterior wing margin, anterior cross vein and third vein was examined and no significant modification was observed. These results suggest that poils au dos does not act through the cis-regulatory sequences controlling expression in the proneural clusters (Gibert, 2005).
To determine which regions of the AS-C are required for the formation of the ectopic bristles in pad, the pad1 mutant was placed in various ac-sc mutant backgrounds. These included several deletions generated by excision of the P-element in the line NP-6066. In(1)ac3, an inversion separating sequences located 1 kb upstream of ac, including the DC enhancer, was used, as well as Df(1)91B (which deletes 45 kb from a position 10.3 kb upstream of sc that includes ac and the DC enhancer); Df(1)115 (which deletes 7.8 kb between the positions 14.5 and 6.7 kb upstream of the scute ATG), and In(1)sc4 (an inversion with a breakpoint 7-8 kb downstream of sc). None of these rearrangements prevent formation of the ectopic bristles present in pad1. In(1)sc4 causes a loss of all scutellar bristles, because the relevant enhancer, located 40 kb downstream of sc, is translocated elsewhere and is thus not able to drive the expression of ac-sc in the scutellum. However, occasional scutellar bristles form in In(1)sc4; pad1 flies at the position normally occupied by the anterior scutellar bristle. In contrast to the rearrangements cited above, no, or very few, ectopic bristles are formed in scbald; pad1 flies. This hypomorphic sc allele carries the remains of a P element located 10 kb upstream of sc and displays a high frequency of missing SC, aDC and orbital bristles. Together, these results indicate that the target sequences are probably located in a fragment that extends 6.7 kb upstream and 7-8 kb downstream of sc (Gibert, 2005).
In order to visualize the precursors of the ectopic bristles in pad1, an antibody against Senseless, a marker of neural precursors, was used. A transgene was used driving the expression of LacZ under the control of the achaete/scute Sensory Organ Precursor enhancer (SOP-lacZ). The minimal SOP enhancer of 500 bp drives expression of lacZ exclusively in the bristle precursors and contains binding sites for Ac-Sc/Da (E boxes), as well as sites for the binding of repressors. It was observed that the precursors of ectopic bristles appear between 0 and 2 h after puparium formation. This is about the same time as the formation of the precursors for the anterior DC (aDC) bristles in wild-type flies. The posterior DC (pDC) precursors appear much earlier, around 24 to 12 h before puparium formation. In situ hybridization with a probe to sc, indicated that sc is expressed ectopically in third instar wing discs. Expression of ac was examined using an anti-Achaete antibody and is also significantly up-regulated in pad1. In both cases, the proneural clusters that give rise to the wild-type bristle precursors are clearly visible at wild-type locations, but they appear to be enlarged. In addition, many more cells express high levels of ac-sc outside the proneural clusters. These are mainly located in the future anterior and central regions of the notum, consistent with the fact that ectopic macrochaetes are found here. Weak sc expression can be detected in these areas in wild-type discs but does not give rise to sense organs. Ectopic expression in pad1 is particularly visible in the region of the presutural, DC and PSA bristles where many ectopic bristles form (Gibert, 2005).
To better visualize the regions of ectopic expression, the reporter construct EE4 containing an artificial SOP enhancer composed of four E-boxes and the binding sites for the Ac and Sc proteins was used. The EE4 construct lacks the sequences required for repression and so it is very sensitive to the levels of Ac-Sc and can be used to measure the increased amounts of Ac-Sc in the pad mutant. It was observed that expression driven by this enhancer in pad1 is significantly different from that seen in the wild type. In the wild type, it is expressed exclusively in the cells of the proneural clusters where it is present at high levels. In pad1, expression in the PSA region expands medially and expression in the DC region expands anteriorly. Some of the ectopic precursors appear within this expanded anterior region (Gibert, 2005).
Using in situ hybridization, the expression pattern of pad was examined in embryos and third instar larval wing discs. In embryos, transcripts accumulate in the central nervous system: staining can be clearly detected above background levels shortly before stage 16. This is consistent with the findings of Brody (2002). No staining could be detected in the larval peripheral nervous system. No staining was detected in the wing discs. This may reflect low levels of ubiquitously expressed transcripts. It is nevertheless believed that pad is expressed in the wing disc since pad1 mutant clones autonomously display ectopic bristles on the notum (Gibert, 2005).
Flies were collected in the garden of Marrakech University in 1999 (Chakir, 2002). A population founded by more than 30 females was selected in bulk for an increased number of thoracic macrochaetes at 17°C for the first few generations and at 25°C later. Chromosomes were extracted from one female Drosophila with a high number (16) of ectopic bristles using balancer chromosomes. It was observed that all the variation is due to the third chromosome. An isogenic line, A10, with the X and second chromosome from a wild-type stock (Oregon R) and the third chromosome from this female was used for the following analysis. This homozygous line is perfectly viable and fertile. The phenotype is recessive: homozygotes have a marked bristle phenotype. At 25°C, females show 13.0 (±2.28) and males 9.38 (±2.55) ectopic bristles. Ectopic bristles are mainly located in the dorso-central (DC) and presutural (PS) regions. The anterior scutellar (aSC), posterior post-alar (pPA) and posterior supra-alar bristles (pSA) are also frequently duplicated in females. Additional bristles are found laterally but less frequently. These are usually slightly shorter and thicker. The density of microchaetes is also increased. There are often four or five sensilla campaniformia on the third vein (L3) of the wing (average 3.45, n = 22) instead of three, and at the location of the twin sensilla of the anterior wing margin (TSM), there are often three sensilla (Gibert, 2005).
The multiply marked third chromosome ru cu ca was used for recombination mapping and a single segment was identified between curled (86D) and stripe (90E) that is responsible for the phenotype. Single nucleotide polymorphism (SNP) mapping, using 30 chromosomes with a break point between curled and striped was used and the location was refined to region 88C-89E. A study of deficiencies showed that Df(3R)sbd26 (89B9-10; 89C7-D1) and Df(3R)P115 (89B13; 89E7) do not complement A10 for the bristle phenotype. The phenotype is thus due to one (or several) loss of function mutations in gene(s) located in the region common to both deletions: 89B13-89D1. There are about 40 genes in this region which spans around 200 kb. In order to map the mutation(s) more precisely, new recombinants were used. To select the potentially informative ones, P insertions were used with a w+ marker located on the left [line MD237 (pnr-Gal4) and tara1] or on the right (insertion in CSN5 and line E7439) of the mutation(s). Females w/w; Pw+/A10 were crossed with males w; A10/A10. More than 5000 flies were screened for each P insertion and flies Pw+A10/A10 and +/A10 were selected. The recombination point was mapped by SNP analysis in these heterozygous flies. Identified and used were polymorphic sites located in the gene sulf1 (SF4, MspI), between sulf1 and CG6901 (ST1, NdeI), between CG17930 and SF2 (CSF, BalI), between CG10817 and ss (SS3, DraI) and between ss and CG31279 (SS5, SspI). The mutation(s) were localized between CSF and SS3. This segment is 36.3 kb long and contains eight genes, none of which had previously been shown to have a role in bristle development. One of them, CG10309, encoding a zinc-finger transcription factor, had been identified (Brody, 2002) in a differential screen for genes highly expressed in the embryonic nervous system (Gibert, 2005).
4289 bp encompassing the CG10309 gene in A10 were sequenced. The sequence is identical to the allele of CG10309 in the publicly available sequence of D. melanogaster genome except for a deletion of 29 bp from position 976 to 1004 (inclusive) downstream of the A of the predicted ATG . A cDNA recently sequenced by the Berkeley Drosophila Genome Project (clone IP01015p) corresponds exactly to the predicted mRNA. The deletion, in the third exon, induces a frameshift and introduces 20 new codons followed by a stop codon. The resulting truncated protein is thus predicted to be 308 aa long instead of 925 aa and would lack the four zinc fingers located in the C-terminal part. This gene was named poils-au-dos (pad) for 'hairy back' in French and A10 is now referred to as pad1 (Gibert, 2005).
In order to verify that the pad phenotype is indeed caused by the mutation in the gene CG10309, and that no other linked mutation contributes to the phenotype, complementation tests were performed. Since no other mutants of CG10309 were available, new alleles were generated by mobilizing a P-element inserted 400 bp from the predicted ATG in the line P(SUPor-P)KG08729 created by the Drosophila Genome Disruption project. Three independent mutant lines were recovered that failed to complement pad1 for the bristle phenotype. All three mutants deleted a large 5' portion of CG10309 transcription unit including the region encoding the ZAD domain. The mutants were named pad2, pad3 and pad4. All three are late pupal lethals, with a few escapers in pad2. In pad3 and pad4, the transcription unit of the neighboring gene SF2 is also disrupted, which correlates with the higher lethality of these mutants compared to pad2. To ascertain whether SF2 is affected in pad1, the whole coding frame of SF2 in the chromosome carrying pad1 was sequenced and no differences were found in the DNA sequence with the published genome sequence. The three new pad alleles have a more extreme bristle phenotype than that of pad1 and, unlike pad1 flies, they also have twisted legs (Gibert, 2005).
The generalized increase in ac-sc expression suggests that poils au dos is involved in the repression of ac-sc. Interactions between pad and other known repressors of ac-sc were tested. pad1 interacts moderately with emcpel and very strongly with hairy1. In h1 homozygotes grown at 18°C, ectopic bristles are occasionally found anterior to the aDC, whereas none were seen at 25°C. In h1 pad1 homozygotes, many ectopic bristles were observed at 25°C at positions where none were seen in either of the single mutants. These include DC bristles closer to the thoracic midline and additional bristles between the anterior and posterior scutellars. Interestingly, most of these ectopic bristles are located in the posterior half of the notum whereas the visible effect of pad alone is in the anterior part of the notum (Gibert, 2005).
Mutations in very few other genes have been shown to induce ectopic bristles in the anterior region of the notum. Some ectopic bristles can be induced in this region by reduction in Dpp signaling late in development. A genetic interaction between pad and Dpp signaling was tested using mutations in the receptors punt (put) and thickveins (tkv). A strong genetic interaction was observed between pad1 and putP1. Trans-heterozygous putP1/pad1 flies have ectopic DC bristles whereas each of the single heterozygotes displays a wild-type pattern. Flies homozygous for the hypomorphic mutation tkv1 occasionally have ectopic bristles anterior to the aDC at 18°C. The phenotype is strongly enhanced in the anterior region of the notum of double mutant tkv1; pad1 flies grown at 25°C. In particular, many more ectopic bristles are visible around the prescutal suture than in pad1 alone (Gibert, 2005).
Search PubMed for articles about Drosophila poils au dos
Balcells, L., Modolell, J. and Ruiz-Gomez, M. (1988). A unitary basis for different Hairy-wing mutations of Drosophila melanogaster. EMBO J. 7(12): 3899-906. 3145198
Brody, T., Stivers, C., Nagle, J. and Odenwald, W. F. (2002). Identification of novel Drosophila neural precursor genes using a differential embryonic head cDNA screen, Mech. Dev. 113: 41-59. 11900973
Chakir, M., Chafik, A., Moreteau, B., Gibert, P. and David, J. R. (2002). Male sterility thermal thresholds in Drosophila: D. simulans appears more cold-adapted than its sibling D. melanogaster. Genetica 114(2): 195-205. 12041832
Chung, H. R., Schafer, U., Jackle, H. and Bohm, S. (2002). Genomic expansion and clustering of ZAD-containing C2H2 zinc-finger genes in Drosophila. EMBO Rep. 3(12): 1158-62. 12446571
Crozatier, M., et al. (1992). Single amino acid exchanges in separate domains of the Drosophila serendipity delta zinc finger protein cause embryonic and sex biased lethality. Genetics 131(4): 905-16. 1516821
Dominguez, A., Albornoz, J., Santiago, E. and Gutierrez, A. (1993). Chromosomal analysis of D. melanogaster long-term selected lines. J. Hered. 84(1): 63-6. 8440889
Fridman, E., Pleban, T. and Zamir, D. (2000). A recombination hotspot delimits a wild-species quantitative trait locus for tomato sugar content to 484 bp within an invertase gene. Proc. Natl. Acad. Sci. 97(9): 4718-23. 10781077
Gaszner, M., Vazquez, J. and Schedl, P. (1999). The Zw5 protein, a component of the scs chromatin domain boundary, is able to block enhancer-promoter interaction. Genes Dev. 13(16): 2098-107. 10465787
Gibert, J. M., Marcellini, S., David, J. R., Schlotterer, C. and Simpson, P. (2005). A major bristle QTL from a selected population of Drosophila uncovers the zinc-finger transcription factor Poils-au-dos, a repressor of achaete-scute. Dev. Biol. 288(1): 194-205. 16216235
Gibert, P., et al. (2004). Comparative analysis of morphological traits among Drosophila melanogaster and D. simulans: genetic variability, clines and phenotypic plasticity. Genetica 120(1-3): 165-79. 15088656
Gurganus, M. C., et al. (1998). Genotype-environment interaction at quantitative trait loci affecting sensory bristle number in Drosophila melanogaster. Genetics 149(4): 1883-98. 9691044
Jauch, R., et al. (2003). The zinc finger-associated domain of the Drosophila transcription factor grauzone is a novel zinc-coordinating protein-protein interaction module. Structure 11(11): 1393-402. 14604529
Long, A. D., Mullaney, S. L., Mackay, T. F. and Langley, C. H. (1996). Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. Genetics 144(4): 1497-510. 8978039
Shapiro, M. D., et al. (2004). Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks. Nature 428(6984): 717-23. 15085123
Skaer, N. and Simpson P. (2000). Genetic analysis of bristle loss in hybrids between Drosophila melanogaster and D. simulans provides evidence for divergence of cis-regulatory sequences in the achaete-scute gene complex. Dev. Biol. 221(1): 148-67. 10772798
date revised: 5 March 2005
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