The Hox gene Abdominal-B antagonizes appendage development in the genital disc of Drosophila.

In Drosophila, the Hox gene Abdominal-B is required to specify the posterior abdomen and the genitalia. Homologues of Abdominal-B in other species are also needed to determine the posterior part of the body. We have studied the function of Abdominal-B in the formation of Drosophila genitalia, and show here that absence of Abdominal-B in the genital disc of Drosophila transforms male and female genitalia into leg or, less frequently, into antenna. These transformations are accompanied by the ectopic expression of genes such as Distal-less or dachshund, which are normally required in these appendages. The extent of wild-type and ectopic Distal-less expression depends on the antagonistic activities of the Abdominal-B gene, as a repressor, and of the decapentaplegic and wingless genes as activators. Absence of Abdominal-B also changes the expression of Homothorax, a Hox gene co-factor. Our results suggest that Abdominal-B forms genitalia by modifying an underlying positional information and repressing appendage development. We propose that the genital primordia should be subdivided into two regions, one of them competent to be transformed into an appendage in the absence of Abdominal-B.

Doublesex Surprises

The Homeotic Complex (Hox) genes encode conserved homeodomain transcription factors that specify segment identity and appendage morphology along the antero-posterior axis in bilaterian animals. The Hox gene Abdominal-B (Abd-B) is mainly expressed in the posterior segments of the abdomen and plays an important role in insect organogenesis. In Mecoptera, the potential function of this gene remains unclear yet. Here, we performed a de novo transcriptome assembly and identified an Abd-B ortholog in the scorpionfly Panorpa liui. Quantitative real-time reverse transcription PCR showed that Abd-B expression increased gradually in embryos 76 h post oviposition, and was mainly present in the more posterior abdominal segments. Embryonic RNA interference of Abd-B resulted in a set of abnormalities, including developmental arrest, malformed suckers and misspecification of posterior segment identity. These results suggest that Abd-B is required for the proper development of the posterior abdomen. Furthermore, in Abd-B RNAi embryos, the expression of the appendage marker Distal-less (Dll) was up-regulated and was additionally present on abdominal segments IX and X compared with wild embryos, suggesting that scorpionfly Abd-B may act to suppress proleg development and has gained the ability to repress Dll expression on the more posterior abdominal segments. This study provides additional information on both the functional and evolutionary roles of Abd-B across different insects.

Drosophila Left/Right Asymmetry Establishment Is Controlled by the Hox Gene Abdominal-B

Development of the genitalia in Drosophila melanogaster

Regulation of Body Pigmentation by the Abdominal-B Hox Protein and Its Gain and Loss in Drosophila Evolution

The elimination of an adult segment by the Hox gene Abdominal-B

Cross-regulation of Hox genes in the Drosophila melanogaster embryo.

The EMBO Workshop on Upstream and Downstream of Hox Genes took place in Hyderabad, India, between 14 and 17 December 2005, and was organized by R. Mishra and F. Karch. ![][1] For many years, EMBO workshops dealing with new insights into the regulation and function of Hox genes have been held in Switzerland. However, last year, the EMBO World Programme, together with the Centre for Cellular and Molecular Biology (CCMB), held a workshop entitled Upstream and Downstream of Hox Genes in the CCMB's hometown of Hyderabad, India. Imagine beautiful gardens full of butterflies and palm trees, a delightful guest house neighbouring a state‐of‐the‐art research centre, all in a peaceful oasis surrounded by a pulsating and crowded Indian city. The question at the beginning of the meeting was whether the talks and discussions would match the stunning environment; it was answered rapidly and affirmatively. Hox genes have had an illustrious and curious history. Perhaps one of the most famous images in biology from the past century is the four‐winged mutant of the fruit fly Drosophila melanogaster caused by mutations in the Hox gene Ultrabithorax ( Ubx ). This fascinating mutant fly, discovered and characterized by Edward B. Lewis, has motivated many investigators to join the field to understand how these genes are responsible for such complex changes in morphology. Another highlight of Hox history was Matthew Scott's, William McGinnis's and Walter Gehring's discovery of the homeodomain—a 60‐amino‐acid DNA‐binding motif now known to be a key domain in hundreds of genes throughout the animal, fungal and plant kingdoms. Although a lot has been learned through experiments stemming from these important discoveries, there are still many open questions. Among the questions being debated in the field and at the meeting are: How is the regulation of the Hox genes initiated and maintained? How do Hox proteins … [1]: /embed/graphic-1.gif

In insects, the Hox gene Abdominal-B (Abd-B) governs the development of the posterior-most segments, the number and fate of which differ within and between orders. A striking feature of insect evolution is a trend toward the reduction of posterior abdominal segments which is most pronounced in higher Diptera. In Drosophila melanogaster, two distinct Abd-B transcript classes and protein isoforms are expressed in non-overlapping domains and have discrete functions in patterning the posterior abdomen. It has been proposed that evolutionary changes in Abd-B structure and expression are responsible for the reduction of the dipteran abdomen. We have investigated the relationship between the evolution of the Abd-B gene and abdominal reduction by analyzing the structure and expression of homologs from four additional dipterans representing distinct clades within the order. The lower dipteran mosquito Anopheles gambiae expresses a single Abd-B transcript class, as do two species phylogenetically intermediate to mosquitoes and drosophilids. These results delimit the evolution of distinct functional Abd-B isoforms to within the dipteran radiation after the origin of the reduced abdominal morphology. Furthermore, we found that the spatial distribution of Abd-B transcripts in non-drosophilid Diptera is identical to the combined domains of the two D. melanogaster Abd-B transcripts. Therefore, neither the structural evolution nor changes in the spatial regulation of Abd-B account for the derived abdomen of higher Diptera. The recent subfunctionalization of this Hox gene has occurred without any apparent morphological correlate. We conclude that regulatory modifications to developmental programs downstream of or parallel to Abd-B are responsible for the evolutionary reduction of the higher dipteran postabdomen.

ABSTRACTHighly conserved DM domain-containing transcription factors (Doublesex/MAB-3/DMRT1) are responsible for generating sexually dimorphic features. In the Drosophila central nervous system, a set of Doublesex (Dsx)-expressing neuroblasts undergo apoptosis in females whereas their male counterparts proliferate and give rise to serotonergic neurons crucial for adult mating behaviour. Our study demonstrates that the female-specific isoform of Dsx collaborates with Hox gene Abdominal-B (Abd-B) to bring about this apoptosis. Biochemical results suggest that proteins AbdB and Dsx interact through their highly conserved homeodomain and DM domain, respectively. This interaction is translated into a cooperative binding of the two proteins on the apoptotic enhancer in the case of females but not in the case of males, resulting in female-specific activation of apoptotic genes. The capacity of AbdB to use the sex-specific isoform of Dsx as a cofactor underlines the possibility that these two classes of protein are capable of cooperating in selection and regulation of target genes in a tissue- and sex-specific manner. We propose that this interaction could be a common theme in generating sexual dimorphism in different tissues across different species.

The Sex Determination Gene doublesex Regulates the A/P Organizer to Direct Sex-Specific Patterns of Growth in the Drosophila Genital Imaginal Disc

The homeotic (Hox) genes are highly conserved in metazoans, where they are required for various processes in development, and misregulation of their expression is associated with human cancer. In the developing embryo, Hox genes are activated sequentially in time and space according to their genomic position within Hox gene clusters. Accumulating evidence implicates both enhancer elements and noncoding RNAs in controlling this spatiotemporal expression of Hox genes, but disentangling their relative contributions is challenging. Here, we identify two cis-regulatory elements (E1 and E2) functioning as shadow enhancers to regulate the early expression of the HoxA genes. Simultaneous deletion of these shadow enhancers in embryonic stem cells leads to impaired activation of HoxA genes upon differentiation, while knockdown of a long noncoding RNA overlapping E1 has no detectable effect on their expression. Although MLL/COMPASS (complex of proteins associated with Set1) family of histone methyltransferases is known to activate transcription of Hox genes in other contexts, we found that individual inactivation of the MLL1-4/COMPASS family members has little effect on early Hox gene activation. Instead, we demonstrate that SET1A/COMPASS is required for full transcriptional activation of multiple Hox genes but functions independently of the E1 and E2 cis-regulatory elements. Our results reveal multiple regulatory layers for Hox genes to fine-tune transcriptional programs essential for development.

An H3K36 Methylation-Engaging Tudor Motif of Polycomb-like Proteins Mediates PRC2 Complex Targeting

In both sexes, the Drosophila genital disc contains the female and male genital primordia. The sex determination gene doublesex controls which of these primordia will develop and which will be repressed. In females, the presence of Doublesex(F) product results in the development of the female genital primordium and repression of the male primordium. In males, the presence of Doublesex(M) product results in the development and repression of the male and female genital primordia, respectively. This report shows that Doublesex(F) prevents the induction of decapentaplegic by Hedgehog in the repressed male primordium of female genital discs, whereas Doublesex(M) blocks the Wingless pathway in the repressed female primordium of male genital discs. It is also shown that Doublesex(F) is continuously required during female larval development to prevent activation of decapentaplegic in the repressed male primordium, and during pupation for female genital cytodifferentiation. In males, however, it seems that Doublesex(M) is not continuously required during larval development for blocking the Wingless signaling pathway in the female genital primordium. Furthermore, Doublesex(M) does not appear to be needed during pupation for male genital cytodifferentiation. Using dachshund as a gene target for Decapentaplegic and Wingless signals, it was also found that Doublesex(M) and Doublesex(F) both positively and negatively control the response to these signals in male and female genitalia, respectively. A model is presented for the dimorphic sexual development of the genital primordium in which both Doublesex(M) and Doublesex(F) products play positive and negative roles.