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751.
Stomata consist of a pair of guard cells that mediate gas and water-vapour exchange between plants and the atmosphere. Stomatal precursor cells-meristemoids-possess a transient stem-cell-like property and undergo several rounds of asymmetric divisions before further differentiation. Here we report that the Arabidopsis thaliana basic helix-loop-helix (bHLH) protein MUTE is a key switch for meristemoid fate transition. In the absence of MUTE, meristemoids abort after excessive asymmetric divisions and fail to differentiate stomata. Constitutive overexpression of MUTE directs the entire epidermis to adopt guard cell identity. MUTE has two paralogues: FAMA, a regulator of guard cell morphogenesis, and SPEECHLESS (SPCH). We show that SPCH directs the first asymmetric division that initiates stomatal lineage. Together, SPCH, MUTE and FAMA bHLH proteins control stomatal development at three consecutive steps: initiation, meristemoid differentiation and guard cell morphogenesis. Our findings highlight the roles of closely related bHLHs in cell type differentiation in plants and animals. 相似文献
752.
The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of T*A and U*A base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases. 相似文献
753.
Dispersal has a significant impact on lifetime reproductive success, and is often more prevalent in one sex than the other. In group-living mammals, dispersal is normally male-biased and in theory this sexual bias could be a response by males to female mate preferences, competition for access to females or resources, or the result of males avoiding inbreeding. There is a lack of studies on social mammals that simultaneously assess these factors and measure the fitness consequences of male dispersal decisions. Here we show that male-biased dispersal in the spotted hyaena (Crocuta crocuta) most probably results from an adaptive response by males to simple female mate-choice rules that have evolved to avoid inbreeding. Microsatellite profiling revealed that females preferred sires that were born into or immigrated into the female's group after the female was born. Furthermore, young females preferred short-tenured sires and older females preferred longer-tenured sires. Males responded to these female mate preferences by initiating their reproductive careers in groups containing the highest number of young females. As a consequence, 11% of males started their reproductive career in their natal group and 89% of males dispersed. Males that started reproduction in groups containing the highest number of young females had a higher long-term reproductive success than males that did not. The female mate-choice rules ensured that females effectively avoided inbreeding without the need to discriminate directly against close kin or males born in their own group, or to favour immigrant males. The extent of male dispersal as a response to such female mate preferences depends on the demographic structure of breeding groups, rather than the genetic relatedness between females and males. 相似文献
754.
BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module 总被引:1,自引:0,他引:1
Park D Tosello-Trampont AC Elliott MR Lu M Haney LB Ma Z Klibanov AL Mandell JW Ravichandran KS 《Nature》2007,450(7168):430-434
Engulfment and subsequent degradation of apoptotic cells is an essential step that occurs throughout life in all multicellular organisms. ELMO/Dock180/Rac proteins are a conserved signalling module for promoting the internalization of apoptotic cell corpses; ELMO and Dock180 function together as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac, and thereby regulate the phagocyte actin cytoskeleton during engulfment. However, the receptor(s) upstream of the ELMO/Dock180/Rac module are still unknown. Here we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a receptor upstream of ELMO and as a receptor that can bind phosphatidylserine on apoptotic cells. BAI1 is a seven-transmembrane protein belonging to the adhesion-type G-protein-coupled receptor family, with an extended extracellular region and no known ligands. We show that BAI1 functions as an engulfment receptor in both the recognition and subsequent internalization of apoptotic cells. Through multiple lines of investigation, we identify phosphatidylserine, a key 'eat-me' signal exposed on apoptotic cells, as a ligand for BAI1. The thrombospondin type 1 repeats within the extracellular region of BAI1 mediate direct binding to phosphatidylserine. As with intracellular signalling, BAI1 forms a trimeric complex with ELMO and Dock180, and functional studies suggest that BAI1 cooperates with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells. Last, decreased BAI1 expression or interference with BAI1 function inhibits the engulfment of apoptotic targets ex vivo and in vivo. Thus, BAI1 is a phosphatidylserine recognition receptor that can directly recruit a Rac-GEF complex to mediate the uptake of apoptotic cells. 相似文献
755.
PTC124 targets genetic disorders caused by nonsense mutations 总被引:1,自引:0,他引:1
Welch EM Barton ER Zhuo J Tomizawa Y Friesen WJ Trifillis P Paushkin S Patel M Trotta CR Hwang S Wilde RG Karp G Takasugi J Chen G Jones S Ren H Moon YC Corson D Turpoff AA Campbell JA Conn MM Khan A Almstead NG Hedrick J Mollin A Risher N Weetall M Yeh S Branstrom AA Colacino JM Babiak J Ju WD Hirawat S Northcutt VJ Miller LL Spatrick P He F Kawana M Feng H Jacobson A Peltz SW Sweeney HL 《Nature》2007,447(7140):87-91
Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options. 相似文献
756.
Stark A Lin MF Kheradpour P Pedersen JS Parts L Carlson JW Crosby MA Rasmussen MD Roy S Deoras AN Ruby JG Brennecke J;Harvard FlyBase curators;Berkeley Drosophila Genome Project Hodges E Hinrichs AS Caspi A Paten B Park SW Han MV Maeder ML Polansky BJ Robson BE Aerts S van Helden J Hassan B Gilbert DG Eastman DA Rice M Weir M Hahn MW Park Y Dewey CN Pachter L Kent WJ Haussler D Lai EC Bartel DP Hannon GJ Kaufman TC Eisen MB Clark AG Smith D Celniker SE Gelbart WM Kellis M 《Nature》2007,450(7167):219-232
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760.
Barker N van Es JH Kuipers J Kujala P van den Born M Cozijnsen M Haegebarth A Korving J Begthel H Peters PJ Clevers H 《Nature》2007,449(7165):1003-1007
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers. 相似文献