Suchergebnisse

Protein farnesyltransferase (FTase) is an enzyme responsible for posttranslational modification of proteins carrying a carboxy-terminal CaaX motif. Farnesylation allows substrates to interact with membranes and protein targets. Using gene-targeted mice, we report that FTase is essential for embryonic development, but dispensable for adult homeostasis. Six-month-old FTase-deficient mice display delayed wound healing and maturation defects in erythroid cells. Embryonic fibroblasts lacking FTase have a flat morphology and reduced motility and proliferation rates. Ablation of FTase in two ras oncogene-dependent tumor models has no significant consequences for tumor initiation. However, elimination of FTase during tumor progression had a limited but significant inhibitory effect. These results should help to better understand the role of protein farnesylation in normal tissues and in tumor development. ; This work was supported by grants from the V Framework Programme of the European Union (QLK3-1999-00875) to M.B. and from the Ministerio de Ciencia y Tecnologia (SAF2001-0058) and Fondo de Investigación Sanitaria (00/0109) to J.V. P.D. was supported by the Association pour la Recherche contre le Cancer (ARC). P.J.C. was supported by NIH grant GM46372. N.M. was supported by a BEFI Fellowship from the Fondo de Investigación Sanitaria. The CNIO is partially supported by the RTICCC (Red de Centros de Cáncer; FIS C03/10)

Downstream of gene expression, effectors such as the actomyosin contractile machinery drive embryo morphogenesis. During $\textit{Drosophila}$ embryonic axis extension, actomyosin has a specific planar-polarised organisation, which is responsible for oriented cell intercalation. In addition to these cell rearrangements, cell shape changes also contribute to tissue deformation. While cell-autonomous dynamics are well described, understanding the tissue-scale behaviour challenges us to solve the corresponding mechanical problem at the scale of the whole embryo, since mechanical resistance of all neighbouring epithelia will feedback on individual cells. Here we propose a novel numerical approach to compute the whole-embryo dynamics of the actomyosin-rich apical epithelial surface. We input in the model specific patterns of actomyosin contractility, such as the planar-polarisation of actomyosin in defined ventro-lateral regions of the embryo. Tissue strain rates and displacements are then predicted over the whole embryo surface according to the global balance of stresses and the material behaviour of the epithelium. Epithelia are modelled using a rheological law that relates the rate of deformation to the local stresses and actomyosin anisotropic contractility. Predicted flow patterns are consistent with the cell flows observed when imaging $\textit{Drosophila}$ axis extension $\textit{in toto}$, using light sheet microscopy. The agreement between model and experimental data indicates that the anisotropic contractility of planar-polarised actomyosin in the ventro-lateral germband tissue can directly cause the tissue-scale deformations of the whole embryo. The three-dimensional mechanical balance is dependent on the geometry of the embryo, whose curved surface is taken into account in the simulations. Importantly, we find that to reproduce experimental flows, the model requires the presence of the cephalic furrow, a fold located anteriorly of the extending tissues. The presence of this geometric feature, through the global mechanical balance, guides the flow and orients extension towards the posterior end. ; All the computations presented in this paper were performed using the Cactus platform of the CIMENT infrastructure (https://ciment.ujf-grenoble.fr), which is supported by Région Rhône-Alpes (GRANT CPER07-13, http://en.rhonealpes.fr/370-the-quality-of-the-research.htm). MD, PS and JE thank Région Rhône-Alpes (CIBLE and IXXI, all authors; CMIRA, JE only), MD thanks Malian government and French embassy in Bamako "Bourse d'Excellences" programme, LIPHY and LJK (CNRS and Univ. Grenoble Alpes) for financial support. MD and JE thank ANR-12-BS09-0020-01 "Transmig" and ANR-11-LABX-0030 "Tec21", and are members of GDR 3570 MecaBio and GDR 3070 CellTiss of CNRS. JE thanks the Isaac Newton Institute for Mathematical Sciences for its hospitality during the programme "Coupling Geometric PDEs with Physics for Cell Morphology, Motility and Pattern Formation" supported by EPSRC Grant Number EP/K032208/1. CML, GBB and BS were supported by Wellcome Trust Investigator Award 099234/Z/12/Z to BS.

12 páginas.-- 6 figuras.-- 45 referencias.-- Supplementary data are available at JXB online doi:10.1093/jxb/erx020 ; HSFA9 is a seed-specific transcription factor that in sunflower (Helianthus annuus) is involved in desiccation tolerance and longevity. Here we show that the constitutive overexpression of HSFA9 in tobacco (Nicotiana tabacum) seedlings attenuated hypocotyl growth under darkness and accelerated the initial photosynthetic development. Plants overexpressing HSFA9 increased accumulation of carotenoids, chlorophyllide, and chlorophyll, and displayed earlier unfolding of the cotyledons. HSFA9 enhanced phytochrome-dependent light responses, as shown by an intensified hypocotyl length reduction after treatments with continuous far-red or red light. This observation indicated the involvement of at least two phytochromes: PHYA and PHYB. Reduced hypocotyl length under darkness did not depend on phytochrome photo-activation; this was inferred from the lack of effect observed using far-red light pulses applied before the dark treatment. HSFA9 increased the expression of genes that activate photomorphogenesis, including PHYA, PHYB, and HY5. HSFA9 might directly upregulate PHYA and indirectly affect PHYB transcription, as suggested by transient expression assays. Converse effects on gene expression, greening, and cotyledon unfolding were observed using a dominant-negative form of HSFA9, which was overexpressed under a seed-specific promoter. This work uncovers a novel transcriptional link, through HSFA9, between seed maturation and early photomorphogenesis. In all, our data suggest that HSFA9 enhances photomorphogenesis via early transcriptional effects that start in seeds under darkness ; This work was supported by the European Regional Development Fund (FEDER) and the Spanish Secretariat of Research, Development, and Innovation (Grants BIO2011-23440 and BIO2014-52303-R). Some additional funds came from the Andalusian Regional Government (Grant BIO148). ; Peer reviewed

15 páginas, 6 figuras.-- et al. ; DNA methylation is a tightly regulated epigenetic mark associated with transcriptional repression. Next-generation sequencing of purified methylated DNA obtained from early Xenopus tropicalis embryos demonstrates that this genome is heavily methylated during blastula and gastrula stages. Although DNA methylation is largely absent from transcriptional start sites marked with histone H3 lysine 4 trimethylation (H3K4me3), we find both promoters and gene bodies of active genes robustly methylated. In contrast, DNA methylation is absent in large H3K27me3 domains, indicating that these two repression pathways have different roles. Comparison with chromatin state maps of human ES cells reveals strong conservation of epigenetic makeup and gene regulation between the two systems. Strikingly, genes that are highly expressed in pluripotent cells and in Xenopus embryos but not in differentiated cells exhibit relatively high DNA methylation. Therefore, we tested the repressive potential of DNA methylation using transient and transgenic approaches and show that methylated promoters are robustly transcribed in blastula- and gastrula-stage embryos, but not in oocytes or late embryos. These findings have implications for reprogramming and the epigenetic regulation of pluripotency and differentiation and suggest a relatively open, pliable chromatin state in early embryos followed by reestablished methylation-dependent transcriptional repression during organogenesis and differentiation. ; This work was funded by grants of the Netherlands Organization of Scientific Research (NWO-ALW VIDI grant 864.03.002) and the U.S. National Institutes of Health (grant R01 HD054356) to G.J.C.V. We thank the Spanish and Andalusian Governments for grants to J.L.G.-S. (BFU2010-14839, Proyecto de Excelencia CVI-3488 and CSD2007-00008) ; Peer reviewed