The xbp-1 gene is essential for development in Drosophila.

International audienceWe report in this paper the characterization of Dxbp-1, the Drosophila homologue of the xpb-1 gene that encodes a "bZIP"-containing transcription factor that plays a key role in the unfolded protein response (UPR), an evolutionarily conserved signalling pathway activated by an overload of misfolded proteins in the endoplasmic reticulum (ER). Dxbp-1 is ubiquitously transcribed, and high levels are found in embryonic salivary glands and in the ovarian follicle cells committed to the synthesis of the respiratory appendages. Loss of function of Dxbp-1 induced a recessive larval lethality, thus, revealing an essential requirement for this gene. The Dxbp-1 transcript was submitted to an "unconventional" splicing that generated a processed Dxbp-1s transcript encoding a DXbp-1 protein isoform, as is the case for yeast, Caenorhabditis elegans and vertebrate hac1/xbp-1 transcripts after UPR activation. However, in the absence of exogenously induced ER stress, the Dxbp-1s transcript was also detectable not only throughout embryonic and larval development but also in adults with a high level of accumulation in the male sexual apparatus and, to a lesser extent, in the salivary glands of the third-instar larvae. Using a Dxbp-1:GFP transgene as an in vivo reporter for Dxbp-1 mRNA unconventional splicing, we confirmed that Dxbp-1 processing took place in the salivary glands of the third-instar larvae. The Dxbp-1 gene appears, thus, to play an essential role during the development of Drosophila, hypothetically by stimulating the folding capacities of the ER in cells committed to intense secretory activities

Integrin-independent repression of cadherin transcription by talin during axis formation in Drosophila.

The Drosophila melanogaster anterior–posterior axis becomes polarized early during oogenesis by the posterior localization of the oocyte within the egg chamber. The invariant position of the oocyte is thought to be driven by an upregulation of the adhesion molecule DE-cadherin in the oocyte and the posterior somatic follicle cells, providing the first in vivo example of cell sorting that is specified by quantitative differences in cell–cell adhesion. However, it has remained unclear how DE-cadherin levels are regulated. Here, we show that talin, known for its role in linking integrins to the actin cytoskeleton, has the unexpected function of specifically inhibiting Decadherin transcription. Follicle cells that are mutant for talin show a strikingly high level of DE-cadherin, due to elevated transcription of DE-cadherin. We demonstrate that this deregulation of DE-cadherin is sufficient to attract the oocyte to lateral and anterior positions. Surprisingly, this function of talin is independent of integrins. These results uncover a new role for talin in regulating cadherin-mediated cell adhesion

Dynamic Expression of Broad-Complex Isoforms Mediates Temporal Control of an Ecdysteroid Target Gene at the Onset of Drosophila Metamorphosis

AbstractMetamorphosis in Drosophila melanogaster is orchestrated by the steroid hormone ecdysone, which triggers a cascade of primary-response transcriptional regulators and secondary effector genes during the third larval instar and prepupal periods of development. The early ecdysone-response Broad-Complex (BR-C) gene, a key regulator of this cascade, is defined by three complementing functions (rbp, br, and 2Bc) and encodes several distinct zinc-finger-containing isoforms (Z1 to Z4). Using isoform-specific polyclonal antibodies we observe in the fat body a switch in BR-C isoform expression from the Z2 to the other three isoforms during the third instar. We show that the 2Bc+ function that corresponds presumably to the Z3 isoform is required for the larval fat body-specific expression of a transgenic construct (AE) in which the lacZ gene is under the control of the ecdysone-regulated enhancer and minimal promoter of the fat body protein 1 (Fbp1) gene. Using hs(BR-C) transgenes, we demonstrate that overexpression of Z1, Z3, or Z4, but not Z2, is able to rescue AE activity with faithful tissue specificity in a BR-C null (npr1) genetic context, demonstrating a partial functional redundancy between Z1, Z3, and Z4 isoforms. We also show that continuous overexpression of Z2 during the third instar represses AE, while conversely, expression of Z3 earlier than its normal onset induces precocious expression of the construct. This finding establishes a tight correlation between the dynamic pattern of expression of the BR-C isoforms and their individual repressive or inductive roles in AE regulation. Altogether our results demonstrate that the balance between BR-C protein isoforms in the fat body mediates, in part, the precise timing of the ecdysone activation of the AE construct but does not modulate its tissue specificity

The promises of neurodegenerative disease modeling.

International audienceThe rise in the prevalence of neurodegenerative diseases parallels the rapid increase in human lifespan. Despite intensive research, the molecular and cellular mechanisms underlying the onset and progression of these devastating diseases with age are still poorly understood. Many aspects of these diseases have been modelled successfully in experimental animals such as the mouse, the zebrafish Brachydanio rero, the nematode worm Caenorhaditis elegans and the fruit fly Drosophila melanogaster. This review will focus on the advantages offered by the genetic tools available in Drosophila for combining powerful strategies in order to tackle the causative factors of these complex pathologies and help to elaborate efficient drugs to treat them

Etude de l'implication de l'histone-acétyltransférase GCN5 dans la régulation de la structure de la chromatine et du développement de Drosophila melanogaster

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Étude du rôle du gène Dfos dans le contrôle de l'architecture des cellules au sein de l'épithélium folliculaire ovarien chez Drosophila melanogaster

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Caractérisation moléculaire et fonctionnelle du gène batman, un nouveau membre des groupes polycomb et trithorax, et étude de l'interférence par l'ARN chez Drosophila melanogaster

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Etude du rôle des gènes Dfos et xbp-1 au cours des réarrangements morphogénétiques de l'épithélium folliculaire ovarien chez Drosophila melanogaster

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF