A Common Mechanism for Antenna-to-Leg Transformation in Drosophila: Suppression of homothorax Transcription by Four HOM-C Genes

Yao, Li-Chin; Liaw, Gwo-Jen; Pai, Chi-Yun; Sun, Yi

doi:10.1006/dbio.1999.9309

Cited by 59 publications

(55 citation statements)

References 56 publications

(63 reference statements)

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“…6N-P). Weaker transformations obtained by the full-length Scr (27,28) support the notion that the synthetic genes exhibit stronger homeotic function in vivo. In the paradigm of salivary gland induction, a morphogenetic process initiated by Scr, the synthetic genes behaved in a predictable way.…”

Section: Discussionmentioning

confidence: 54%

“…Both the fly Scr gene and its functional mouse homolog Hox-a5 (previously described as Hox-1.3) have been shown to induce partial antenna-to-tarsus transformations in the fly head (27,28). To examine the ability of Scr-HD wt and Scr- HD AA to trigger homeotic transformations in vivo we expressed them ectopically in the antennal portion of the eye-antennal disc using the Distalless (Dll) enhancer (29).…”

Section: Resultsmentioning

confidence: 99%

“…The genetic role of Hox genes has been studied extensively by gain-and loss-of-function experiments (24,27,35,(44)(45)(46), and the properties of the HD-DNA complex have been elucidated in solution by NMR (43). Nevertheless, the precise mechanisms that orchestrate the transcriptional regulation of the vast number of Hox target genes remain elusive.…”

Section: Discussionmentioning

confidence: 99%

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Function and specificity of synthetic Hox transcription factors in vivo

Papadopoulos

Vukojević

Adachi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Homeotic (Hox) genes encode transcription factors that confer segmental identity along the anteroposterior axis of the embryo. However the molecular mechanisms underlying Hox-mediated transcription and the differential requirements for specificity in the regulation of the vast number of Hox-target genes remain ill-defined. Here we show that synthetic Sex combs reduced (Scr) genes that encode the Scr C terminus containing the homedomain (HD) and YPWM motif (Scr-HD) are functional in vivo. Synthetic Scr-HD peptides can induce ectopic salivary glands in the embryo and homeotic transformations in the adult fly, act as transcriptional activators and repressors during development, and participate in protein-protein interactions. Their transformation capacity was found to be enhanced over their full-length counterpart and mutations known to transform the full-length protein into constitutively active or inactive variants behaved accordingly in the synthetic peptides. Our results show that synthetic Scr-HD genes are sufficient for homeotic function in Drosophila and suggest that the N terminus of Scr has a role in transcriptional potency, rather than specificity. We also demonstrate that synthetic peptides behave largely in a predictable way, by exhibiting Scr-specific phenotypes throughout development, which makes them an important tool for synthetic biology.synthetic genes | transcriptional specificity | Hox genes | Sex combs reduced | homeotic transformations H omeotic genes code for transcription factors that play an instrumental role in animal development by specifying the identity of body segments along the anteroposterior axis of the embryo (1-4). Hox genes have persisted in the animal kingdom; they are found in animals as diverse as worms and humans (5, 6) and the Homeodomain (HD), a helix-turn-helix DNA-binding domain, has been strikingly conserved in animals since before the bilaterian split (1,7,8). Sequence-specific binding of Hox proteins has been studied for the Drosophila Sex combs reduced (Scr) (9, 10), Antennapedia (Antp) (11, 12) and Ultrabithorax (Ubx) (11, 12) HDs. A consensus sequence TAATC/GC/G recognition core was identified in all of them, which alone is obviously not sufficient to confer transcriptional specificity, because it occurs statistically every kilobase in the genome. Similar sequence preferences have been identified for Deformed (Dfd) and Abdominal-B (Abd-B) (11), raising the question of how target specificity is achieved among different Hox paralogs.A closer look into conserved residues outside the HD identified its amino-terminal YPWM motif that is present in almost all Hox proteins, from flies to vertebrates [with the exception of Abdominal-B (Abd-B), which has conserved only the tryptophan at position 3] (13). Extradenticle (Exd) and its mammalian homolog Pbx1 (14) were found to interact specifically with the YPWM motif of Hox proteins in vitro (15) and crystallographic analysis of a Ubx-Exd complex determined the topology of this interaction (16). Recently the link between the Ant...

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Function and specificity of synthetic Hox transcription factors in vivo

Papadopoulos

Vukojević

Adachi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…homothorax: homothorax is a homeodomain transcription factor required for normal development of proximal leg segments in T. castaneum (Angelini et al 2012), D. melanogaster (Abu-Shaar and Mann 1998; Wu and Cohen 1999;Yao et al 1999), and other insects (Angelini and Kaufman 2004;Ronco et al 2008). It is one of the leg gap genes (Rauskolb 2001).…”

Section: Maxillae and Labiummentioning

confidence: 99%

Patterning of the Adult Mandibulate Mouthparts in the Red Flour Beetle, Tribolium castaneum

et al. 2012

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Specialized insect mouthparts, such as those of Drosophila, are derived from an ancestral mandibulate state, but little is known about the developmental genetics of mandibulate mouthparts. Here, we study the metamorphic patterning of mandibulate mouthparts of the beetle Tribolium castaneum, using RNA interference to deplete the expression of 13 genes involved in mouthpart patterning. These data were used to test three hypotheses related to mouthpart development and evolution. First, we tested the prediction that maxillary and labial palps are patterned using conserved components of the leg-patterning network. This hypothesis was strongly supported: depletion of Distal-less and dachshund led to distal and intermediate deletions of these structures while depletion of homothorax led to homeotic transformation of the proximal maxilla and labium, joint formation required the action of Notch signaling components and odd-skipped paralogs, and distal growth and patterning required epidermal growth factor (EGF) signaling. Additionally, depletion of abrupt or pdm/nubbin caused fusions of palp segments. Second, we tested hypotheses for how adult endites, the inner branches of the maxillary and labial appendages, are formed at metamorphosis. Our data reveal that Distal-less, Notch signaling components, and odd-skipped paralogs, but not dachshund, are required for metamorphosis of the maxillary endites. Endite development thus requires components of the limb proximal-distal axis patterning and joint segmentation networks. Finally, adult mandible development is considered in light of the gnathobasic hypothesis. Interestingly, while EGF activity is required for distal, but not proximal, patterning of other appendages, it is required for normal metamorphic growth of the mandibles.

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“…In the antennal disc, where Antp and the other homeotic genes are not expressed, hth is not repressed and together with Dll defines antennal identity (Dong et al, 2000). It was previously reported that ectopic expression of Antp, or any of the other homeotic proteins, in the antennal disc leads to repression of hth expression and homeotic transformation of the antenna toward leg identity (Casares and Mann, 1998;Yao et al, 1999).…”

Section: Loss Of Asx Function Leads To De-repression Of Antp In the Amentioning

confidence: 99%

Additional sex combs affects antennal development by means of spatially restricted repression of Antp and Wg

Halachmi¹,

Schulze²,

Inbal³

et al. 2007

Developmental Dynamics

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Additional sex combs (Asx) is thought to function in protein complexes of both the Trithorax and Polycomb groups, but very little is known about its developmental roles. Here, we present a detailed analysis of Asx's role in antennal development. We show that loss of Asx in the antennal disc causes a complex phenotype, which consists of distal antenna-to-leg transformations and outgrowth of ectopic leg-like appendages from the Dpp-expressing domain of the disc. Our analyses suggest that these phenotypes are caused mainly by segment-specific de-repression of Antp and expansion of wg expression. We thus conclude that Asx functions normally to repress Antp and to restrict wg expression in specific regions of the developing disc. We also show that, in the absence of Asx's function, Antp expression does not lead to efficient repression of the antennal-determining gene hth, suggesting that Asx is also required for the repression of hth by Antp.

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A Common Mechanism for Antenna-to-Leg Transformation in Drosophila: Suppression of homothorax Transcription by Four HOM-C Genes

Cited by 59 publications

References 56 publications

Function and specificity of synthetic Hox transcription factors in vivo

Function and specificity of synthetic Hox transcription factors in vivo

Patterning of the Adult Mandibulate Mouthparts in the Red Flour Beetle, Tribolium castaneum

Additional sex combs affects antennal development by means of spatially restricted repression of Antp and Wg

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