Assisting Hox proteins in controlling body form: are there new lessons from flies (and mammals)?

Mahaffey, James W.

doi:10.1016/j.gde.2005.06.009

Cited by 18 publications

(17 citation statements)

References 49 publications

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“…What could be the molecular mechanism by which EcR activation impinges on AbdA activity? Given the pivotal role played by transcriptional cofactors in Hox function (Mann and Affolter, 1998;Mahaffey, 2005), one hypothesis is that EcR activates or represses such a Hox cofactor. Exd/Hth are obvious candidates (Mann and Affolter, 1998) but do not seem to be involved; they are not expressed in the cardiac myocytes, neither during embryogenesis (Perrin et al, 2004) nor during the remodelling process (B.M., unpublished).…”

Section: Discussionmentioning

confidence: 99%

Steroid-dependent modification of Hox function drives myocyte reprogramming in theDrosophilaheart

et al. 2005

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In the Drosophila larval cardiac tube, aorta and heart differentiation are controlled by the Hox genes Ultrabithorax(Ubx) and abdominal A (abdA), respectively. There is evidence that the cardiac tube undergoes extensive morphological and functional changes during metamorphosis to form the adult organ, but both the origin of adult cardiac tube myocytes and the underlying genetic control have not been established. Using in vivo time-lapse analysis, we show that the adult fruit fly cardiac tube is formed during metamorphosis by the reprogramming of differentiated and already functional larval cardiomyocytes,without cell proliferation. We characterise the genetic control of the process, which is cell autonomously ensured by the modulation of Ubxexpression and AbdA activity. Larval aorta myocytes are remodelled to differentiate into the functional adult heart, in a process that requires the regulation of Ubx expression. Conversely, the shape, polarity,function and molecular characteristics of the surviving larval contractile heart myocytes are profoundly transformed as these cells are reprogrammed to form the adult terminal chamber. This process is mediated by the regulation of AbdA protein function, which is successively required within these persisting myocytes for the acquisition of both larval and adult differentiated states. Importantly, AbdA specificity is switched at metamorphosis to induce a novel genetic program that leads to differentiation of the terminal chamber. Finally, the steroid hormone ecdysone controls cardiac tube remodelling by impinging on both the regulation of Ubx expression and the modification of AbdA function. Our results shed light on the genetic control of one in vivo occurring remodelling process, which involves a steroid-dependent modification of Hox expression and function.

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Section: Discussionmentioning

confidence: 99%

Steroid-dependent modification of Hox function drives myocyte reprogramming in theDrosophilaheart

et al. 2005

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“…The pattern of expression of ZFPIP overlaps with that of Pbx1 in embryo, suggesting that it could function along with Pbx1 throughout development. A growing body of evidence suggests that a global network of conserved C2H2 zinc finger transcription factors may contribute to the patterning of the embryo in partnership with Hox proteins (Mahaffey, 2005). Thus, ZFPIP is likely to impact on Hox/Pbx function in vivo, so we are currently investigating the genetic and physiological interaction between ZFPIP and Hox/Pbx proteins.…”

Section: Non-homeodomain Containing Proteinsmentioning

confidence: 99%

PBX proteins: much more than Hox cofactors

Laurent¹,

Bihan²,

Omilli³

et al. 2008

Int. J. Dev. Biol.

101

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“…Subsequently, it was shown that the phenotypic suppression of the homeobox gene empty spiracles (ems) is prevented by buttonhead (btd), a gene encoding a zinc finger class transcription factor, correlated with protein interactions between EMS and BTD in vitro (35). Although the structural details of this interaction have to be clarified, it appears that a Hox-zinc finger protein interactions may also be systemic (36). These converging observations may be indicate an entire network of protein-protein interactions among transcription factors, superimposed on the transcriptional networks controlled by these genes and essential for the specification of the different developmental pathways.…”

Section: Cross-regulatory Protein-protein Interactions Among Transcrimentioning

confidence: 99%

Cross-regulatory protein–protein interactions between Hox and Pax transcription factors

Plaza

Prince

Adachi

et al. 2008

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

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Homeotic Hox selector genes encode highly conserved transcriptional regulators involved in the differentiation of multicellular organisms. Ectopic expression of the Antennapedia (ANTP) homeodomain protein in Drosophila imaginal discs induces distinct phenotypes, including an antenna-to-leg transformation and eye reduction. We have proposed that the eye loss phenotype is a consequence of a negative posttranslational control mechanism because of direct protein-protein interactions between ANTP and Eyeless (EY). In the present work, we analyzed the effect of various ANTP homeodomain mutations for their interaction with EY and for head development. Contrasting with the eye loss phenotype, we provide evidence that the antenna-to-leg transformation involves ANTP DNA-binding activity. In a complementary genetic screen performed in yeast, we isolated mutations located in the N terminus of the ANTP homeodomain that inhibit direct interactions with EY without abolishing DNA binding in vitro and in vivo. In a bimolecular fluorescence complementation assay, we detected the ANTP-EY interaction in vivo, these interactions occurring through the paired domain and/or the homeodomain of EY. These results demonstrate that the homeodomain supports multiple molecular regulatory functions in addition to protein-DNA and protein-RNA interactions; it is also involved in protein-protein interactions. Drosophila ͉ antagonism ͉ regulation H omeotic Hox genes are selector genes that generate morphological diversity along the antero-posterior body axis during animal development (1). They encode highly conserved transcription factors defining various cellular identities in the body segments along the antero-posterior axis of the embryo (2, 3). Hox genes share a common sequence element of 180 bp, the homeobox, first isolated in Drosophila (4, 5), encoding a 60-aa homeodomain (HD) DNA-binding domain. The HD presents a stereotypical three ␣-helical structure, and its mode of interaction with DNA is largely invariant. The amino acid 50, a glutamine signature for the Hox proteins, plays a fundamental role in DNA-binding specificity (6). Hox factors have very similar DNA-binding properties (7). Therefore, the limited sequence selectivity of the HD is not sufficient to explain the diversity of cell types and the batteries of downstream genes under the control of Hox proteins. Consequently, elucidating the mechanisms of Hox protein function is critical for understanding development and the diversification of serially homologous structures. Several studies have indicated that Hox factors cooperate with signaling pathways and act with cofactors that modify DNA binding and activation/repression properties (8-10). To date, the best-known Hox cofactors are the Drosophila extradenticle (EXD/PBX) and homothorax (HTH/Meis) proteins. EXD was shown to modulate the DNA-binding specificity and the activity of Hox proteins (11-13), whereas HTH promotes EXD translocation into the nucleus where they participate in a DNA-bound HOX/EXD/HTH ternary complex (14). Altho...

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Assisting Hox proteins in controlling body form: are there new lessons from flies (and mammals)?

Cited by 18 publications

References 49 publications

Steroid-dependent modification of Hox function drives myocyte reprogramming in theDrosophilaheart

Steroid-dependent modification of Hox function drives myocyte reprogramming in theDrosophilaheart

PBX proteins: much more than Hox cofactors

Cross-regulatory protein–protein interactions between Hox and Pax transcription factors

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