Lettre à la rédactionMonsieur le président, Au travers de cette lettre à la rédaction de Radioprotection, nous tenons à vous faire part, pour réflexion, de la note de Martin Enserink publiée dans la prestigieuse revue américaine Science (Vol.312 du 9 juin 2006) intitulé : « Vingt ans après Tchernobyl, des retombées judiciaires tardives ».Cet auteur rappelle tout d'abord que le souvenir de Tchernobyl a commencé à s'estomper dans la plupart des pays d'Europe de l'Ouest, mais pas en France, où le débat fait encore rage au sujet de l'attitude du gouvernement dans les jours qui ont suivi l'explosion, en Ukraine, du réacteur nucléaire de Tchernobyl en 1986.La mise en examen récente de Mr Pellerin montre que le débat est entré dans une nouvelle phase, judiciaire.

Gene regulation by AP-1 transcription factors in response to Jun N-terminal kinase (JNK) signaling controls essential cellular processes during development and in pathological situations. Here, we report genetic and molecular evidence that the histone acetyltransferase (HAT) Chameau and the histone deacetylase DRpd3 act as antagonistic cofactors of DJun and DFos to modulate JNK-dependent transcription during thorax metamorphosis and JNK-induced apoptosis in Drosophila. We demonstrate in cultured cells that DFos phosphorylation mediated by JNK signaling plays a central role in coordinating the dynamics of Chameau and DRpd3 recruitment and function at AP-1-responsive promoters. Activating the pathway stimulates the HAT function of Chameau, promoting histone H4 acetylation and target gene transcription. Conversely, in response to JNK signaling inactivation, DRpd3 is recruited and suppresses histone acetylation and transcription. This study establishes a direct link among JNK signaling, DFos phosphorylation, chromatin modification, and AP-1-dependent transcription and its importance in a developing organism.

The transcription factor dMyc is the sole Drosophila ortholog of the vertebrate c-myc protooncogenes and a central regulator of growth and cell-cycle progression during normal development. We have investigated the molecular basis of dMyc function by analyzing its interaction with the putative transcriptional cofactors Tip48/Reptin (Rept) and Tip49/Pontin (Pont). We demonstrate that Rept and Pont have conserved their ability to bind to Myc during evolution. All three proteins are required for tissue growth in vivo, because mitotic clones mutant for either dmyc, pont,or rept suffer from cell competition. Most importantly, pont shows a strong dominant genetic interaction with dmyc that is manifested in the duration of development, rates of survival and size of the adult animal and, in particular, of the eye. The molecular basis for these effects may be found in the repression of certain target genes, such as mfas, by dMyc:Pont complexes. These findings indicate that dMyc:Pont complexes play an essential role in the control of cellular growth and proliferation during normal development.

Hox proteins provide axial positional information and control segment morphology in development and evolution. Yet how they specify morphological traits that confer segment identity and how axial positional information interferes with intrasegmental patterning cues during organogenesis remain poorly understood. We have investigated the control of Drosophila posterior spiracle morphogenesis, a segment-specific structure that forms under Abdominal-B (AbdB) Hox control in the eighth abdominal segment (A8). We show that the Hedgehog (Hh), Wingless (Wg) and Epidermal Growth Factor Receptor (Egfr) pathways provide specific inputs for posterior spiracle morphogenesis and act in a genetic network made of multiple and rapidly evolving Hox/signalling interplays. A major function of AbdB during posterior spiracle organogenesis is to reset A8 intrasegmental patterning cues, first by reshaping wg and rhomboid expression patterns, then by reallocating the Hh signal and later by initiating de novo expression of the posterior compartment gene engrailed in anterior compartment cells. These changes in expression patterns confer axial specificity to otherwise reiteratively used segmental patterning cues, linking intrasegmental polarity and acquisition of segment identity.

Hox genes encode evolutionarily conserved transcription factors with key functions in development and evolution. Although the multitude of processes individually controlled by Hox proteins highlights the importance of contextual information in setting their diverse activities, the underlying molecular mechanisms still remain elusive. A recent study identified novel Hox molecular partners, whose properties set a conceptual framework to understand how Hox proteins use and integrate contextual information.

The Hox family transcription factors control diversified morphogenesis during development and evolution. They function in concert with Pbc cofactor proteins. Pbc proteins bind the Hox hexapeptide (HX) motif and are thereby thought to confer DNA binding specificity. Here we report that mutation of the AbdA HX motif does not alter its binding site selection but does modify its transregulatory properties in a gene-specific manner in vivo. We also show that a short, evolutionarily conserved motif, PFER, in the homeodomain-HX linker region acts together with the HX to control an AbdA activation/repression switch. Our in vivo data thus reveal functions not previously anticipated from in vitro analyses for the hexapeptide motif in the regulation of Hox activity.

La radioactivité est omniprésente dans notre environnement, et jusque dans notre propre corps. Nous allons tenter dans cet article de répondre à quelques-unes des questions les plus fréquemment posées sur les faibles doses de radioactivité d'origine humaine (ou liées aux comportements de l'homme) en les comparant aux radioactivités d'origine naturelle de niveau souvent comparables, voire supérieures. Bien que, sur un plan strictement scientifique, il faudrait disposer d'études épidémiologiques approfondies pour conclure de façon définitive, ces comparaisons nous amèneront à suggérer qu'il n'y a vraisemblablement aucun effet sur la santé lorsque les doses d'origine humaine sont inférieures aux variations courantes d'un point à un autre de la radioactivité naturelle.

Hox proteins play fundamental roles in generating pattern diversity during development and evolution, acting in broad domains but controlling localized cell diversification and pattern. Much remains to be learned about how Hox selector proteins generate cell-type diversity. In this study, regulatory specificity was investigated by dissecting the genetic and molecular requirements that allow the Hox protein Abdominal A to activate wingless in only a few cells of its broad expression domain in the Drosophila visceral mesoderm. We show that the Dpp/Tgfβ signal controls Abdominal A function, and that Hox protein and signal-activated regulators converge on a wingless enhancer. The signal, acting through Mad and Creb, provides spatial information that subdivides the domain of Abdominal A function through direct combinatorial action, conferring specificity and diversity upon Abdominal A activity.

Hox genes encode evolutionarily conserved transcription factors that play fundamental roles in the organization of the animal body plan. Molecular studies emphasize that unidentified genes contribute to the control of Hox activity. In this study, we describe a genetic screen designed to identify functions required for the control of the wingless (wg) and empty spiracles (ems) target genes by the Hox Abdominal-A and Abdominal-B proteins. A collection of chromosomal deficiencies were screened for their ability to modify GFP fluorescence patterns driven by Hox response elements (HREs) from wg and ems. We found 15 deficiencies that modify the activity of the ems HRE and 18 that modify the activity of the wg HRE. Many deficiencies cause ectopic activity of the HREs, suggesting that spatial restriction of transcriptional activity is an important level in the control of Hox gene function. Further analysis identified eight loci involved in the homeotic regulation of wg or ems. A majority of these modifier genes correspond to previously characterized genes, although not for their roles in the regulation of Hox targets. Five of them encode products acting in or in connection with signal transduction pathways, which suggests an extensive use of signaling in the control of Hox gene function.

Cell motility is regulated by extracellular cues and by intracellular factors that accumulate at sites of contact between cells and the extracellular matrix. One of these factors, focal adhesion kinase (FAK), regulates the cycle of focal adhesion formation and disassembly that is required for cell movement to occur. Recently, Wnt signaling has also been implicated in the control of cell movement in vertebrates, but the mechanism through which Wnt proteins influence motility is unclear. We demonstrate that Drosphila Wnt4 is required for cell movement and FAK regulation during ovarian morphogenesis. Dfrizzled2, Disheveled, and protein kinase C are also required. The DWnt4 cell motility pathway is distinct from both the canonical Wnt pathway and the planar polarity pathway. Our data suggest that DWnt4 facilitates motility through regulation of focal adhesions.

Les genes Hox, acteurs cles du developpement, codent pour des facteurs de transcription conserves au cours de l'evolution dont l'activite determine la diversite de forme et de fonction le long de l'axe antero-posterieur chez les metazoaires. Depuis la decouverte de l'homeodomaine voila aujourd'hui plus de quinze ans, subsiste le paradoxe de proteines presentant des proprietes intrinseques de liaison a l'ADN tres similaires qui enclenchent cependant des programmes developpementaux parfaitement distincts. Dans cette revue, nous traiterons des mecanismes qui permettent aux differentes proteines Hox d'acquerir des fonctions specifiques in vivo et discuterons dans quelle mesure les avancees recentes ouvrent des perspectives nouvelles vers une meilleure comprehension du mode d'action des proteines Hox.

Hox complex genes are key developmental regulators highly conserved throughout evolution. They encode transcription factors that initiate genetic programs of diversified morphogenesis along the anteroposterior embryonic axis. We report the characterization of the novel Drosophila Hox target gene dlarp, isolated from a further screen of a previously described library of genomic DNA fragments associated in vivo with Ultrabithorax proteins. The dlarp spatio-temporal pattern of transcription in wild-type and homeotic mutant embryos is consistent with a positive regulation by Sex combs reduced and Ultrabithorax in the parasegment 2 ectoderm and the abdominal mesoderm, respectively. The teashirt gene product, thought to act in concert with Hox proteins, is also required for the transcriptional control of this target. Search in databases revealed that dlarp has been highly conserved during evolution. The embryonic expression pattern of the mouse orthologue does not support a function downstream of Hox proteins. It is mainly transcribed in neural structures and in developing organs characterized by epithelial-mesenchymal interactions. Dev Dyn 2000;218:401–413. © 2000 Wiley-Liss, Inc.

Small GTPases of the rho family function as signal transducer for extra-cellular stimuli to control cytoskeletal re-organization and a variety of other cellular processes including adhesion, proliferation and transcriptional regulation (Hall, A., 1998. RhoGTPases and the actin cytoskeleton. Science 279, 509-514). Usually widely expressed, their activities are tightly controlled by conformational changes induced by hydrolysis of the GTP bound molecule (Bourne H.R., Sanders D.A., 1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348, 125-132). Conversion of GTP to GDP relies on a rho intrinsic GTPase domain that requires GTPase activating proteins (GAPs) for potent activity (Lamarche, N., Hall. A., 1994. GAPs for rho-related GTPases. Trends Genet. 10, 436-440). Here we report on the identification of a novel Drosophila GAP gene, d-CdGAPr, encoding a protein related to mammalian CdGAPs. The gene is expressed throughout development as well as in adults. Spatio-temporal transcription pattern of d-CdGAPr during embryogenesis is highly dynamic. Abundant in the pre-blastoderm embryo prior to the onset of zygotic transcription, messengers accumulate at the blastoderm posterior pole after cellularisation. During gastrulation and subsequent development, all cells accumulate low levels of d-CdGAPr RNA, while a few territories transiently display stronger expression. Sites of preferential expression include the posterior pole of the early cellular blastoderm, the neuro-ectoderm prior to neuroblast delamination, rows of epidermal cells in the most posterior part of thoracic and first abdominal segments and a ring of epidermal cells at the posterior end of the embryo.

Hox genes encode evolutionarily conserved transcription factors that control the morphological diversification along the anteroposterior (A/P) body axis. Expressed in precise locations in the ectoderm, mesoderm, and endoderm, Hox proteins have distinct regulatory activities in different tissues. How Hox proteins achieve tissue-specific functions and why cells lying at equivalent A/P positions but in different germ layers have distinctive responses to the same Hox protein remains to be determined. Here, we examine this question by identifying parts of Hox proteins necessary for Hox function in different tissues. Available genetic markers allow the regulatory effects of two Hox proteins, Abdominal-A (AbdA) and Ultrabithorax (Ubx), to be distinguished in the Drosophila embryonic epidermis and visceral mesoderm (VM). Chimeric Ubx/AbdA proteins were tested in both tissues and used to identify protein sequences that endow AbdA with a different target gene specificity from Ubx. We found that distinct protein sequences define AbdA, as opposed to Ubx, function in the epidermis vs. the VM. These sequences lie mostly outside the homeodomain (HD), emphasizing the importance of non-HD residues for specific Hox activities. Hox tissue specificity is therefore achieved by sensing distinct Hox protein structures in different tissues.