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A blood cell type termed crystal cell in Drosophila functions in clotting and wound healing and requires Notch for specification and maintenance. We report that crystal cells express elevated levels of Sima protein orthologous to mammalian hypoxia-inducible factor-α (Hif-α) even under conditions of normal oxygen availability. In these platelet-like crystal cells, Sima activates full-length Notch receptor signaling via a noncanonical, ligand-independent mechanism that promotes hemocyte survival during both normal hematopoietic development and hypoxic stress. This interaction initiates in early endosomes, is independent of Hif-β (Τangο in Drosophila), and does not activate hypoxia response targets. Studies in vertebrate myeloid cells have shown a similar up-regulation of Hif-α protein in well-oxygenated environments. This study provides a mechanistic paradigm for Hif-α/Notch interaction that may be conserved in mammals.  相似文献   

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The adult Drosophila midgut contains multipotent intestinal stem cells (ISCs) scattered along its basement membrane that have been shown by lineage analysis to generate both enterocytes and enteroendocrine cells. ISCs containing high levels of cytoplasmic Delta-rich vesicles activate the canonical Notch pathway and down-regulate Delta within their daughters, a process that programs these daughters to become enterocytes. ISCs that express little vesiculate Delta, or are genetically impaired in Notch signaling, specify their daughters to become enteroendocrine cells. Thus, ISCs control daughter cell fate by modulating Notch signaling over time. Our studies suggest that ISCs actively coordinate cell production with local tissue requirements by this mechanism.  相似文献   

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The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity. All 24 putative gating charges of the vertebrate protein are in identical positions in the Drosophila gene. Ten introns interrupt the coding regions of the four homology units; introns with positions conserved among homology units bracket a region hypothesized to be the selectivity filter for the channel. The Drosophila gene maps to the right arm of the second chromosome in region 60D-E. This position does not coincide with any known mutations that confer behavioral phenotypes, but is close to the seizure locus (60A-B), which has been hypothesized to code for a voltage-sensitive sodium channel.  相似文献   

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Transposition of cloned P elements into Drosophila germ line chromosomes   总被引:123,自引:0,他引:123  
Recombinant DNA carrying the 3-kilobase transposable element was injected into Drosophila embryos of a strain that lacked such elements. Under optimum conditions, half of the surviving embryos showed evidence of P element-induced mutations in a fraction of their progeny. Direct analysis of the DNA of strains derived from such flies showed them to contain from one to five intact 3-kilobase P elements located at a wide variety of chromosomal sites. DNA sequences located outside the P element on the injected DNA were not transferred. Thus P elements can efficiently and selectively transpose from extrachromosomal DNA to the DNA of germ line chromosomes in Drosophila embryos. These observations provide the basis for efficient DNA-mediated gene transfer in Drosophila.  相似文献   

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Okajima T  Xu A  Lei L  Irvine KD 《Science (New York, N.Y.)》2005,307(5715):1599-1603
Notch proteins are receptors for a conserved signaling pathway that affects numerous cell fate decisions. We found that in Drosophila, Protein O-fucosyltransferase 1 (OFUT1), an enzyme that glycosylates epidermal growth factor-like domains of Notch, also has a distinct Notch chaperone activity. OFUT1 is an endoplasmic reticulum protein, and its localization was essential for function in vivo. OFUT1 could bind to Notch, was required for the trafficking of wild-type Notch out of the endoplasmic reticulum, and could partially rescue defects in secretion and ligand binding associated with Notch point mutations. This ability of OFUT1 to facilitate folding of Notch did not require its fucosyltransferase activity. Thus, a glycosyltransferase can bind its substrate in the endoplasmic reticulum to facilitate normal folding.  相似文献   

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Upon fertilization, remodeling of condensed maternal and paternal gamete DNA occurs to form the diploid genome. In Xenopus laevis, nucleoplasmin 2 (NPM2) decondenses sperm DNA in vitro. To study chromatin remodeling in vivo, we isolated mammalian NPM2 orthologs. Mouse NPM2 accumulates in oocyte nuclei and persists in preimplantation embryos. Npm2 knockout females have fertility defects owing to failed preimplantation embryo development. Although sperm DNA decondensation proceeds without NPM2, abnormalities are evident in oocyte and early embryonic nuclei. These defects include an absence of coalesced nucleolar structures and loss of heterochromatin and deacetylated histone H3 that normally circumscribe nucleoli in oocytes and early embryos, respectively. Thus, Npm2 is a maternal effect gene critical for nuclear and nucleolar organization and embryonic development.  相似文献   

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The "segmentation clock" is thought to coordinate sequential segmentation of the body axis in vertebrate embryos. This clock comprises a multicellular genetic network of synchronized oscillators, coupled by intercellular Delta-Notch signaling. How this synchrony is established and how its loss determines the position of segmentation defects in Delta and Notch mutants are unknown. We analyzed the clock's synchrony dynamics by varying strength and timing of Notch coupling in zebra-fish embryos with techniques for quantitative perturbation of gene function. We developed a physical theory based on coupled phase oscillators explaining the observed onset and rescue of segmentation defects, the clock's robustness against developmental noise, and a critical point beyond which synchrony decays. We conclude that synchrony among these genetic oscillators can be established by simultaneous initiation and self-organization and that the segmentation defect position is determined by the difference between coupling strength and noise.  相似文献   

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Genes involved in late specification of the mandibular arch, the source of the vertebrate jaw, are expressed with similar patterns in the oral regions of chick and lamprey embryos. However, morphological comparisons indicate that apparently orthologous homeobox genes were expressed in different subdivisions of the ectomesenchyme in the two species. Therefore, the homology and gene expression of the oral region are uncoupled during the transition from agnathan to gnathostome; we conclude that a heterotopic shift of tissue interaction was involved in the evolution of the jaw.  相似文献   

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A family of putative potassium channel genes in Drosophila   总被引:21,自引:0,他引:21  
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Specification of cell fate in the compound eye of Drosophila appears to be controlled entirely by cell interactions. The sevenless gene is required for the correct determination of one of the eight photoreceptor cells (R7) in each ommatidium. It encodes a transmembrane protein with a tyrosine kinase domain and is expressed transiently on a subpopulation of ommatidial precursor cells including the R7 precursors. It is shown here that heat shock-induced indiscriminate expression of a sevenless complementary DNA throughout development can correctly specify R7 cell identity without affecting the development of other cells. Furthermore, discontinuous supply of sevenless protein during eye development leads to the formation of mosaic eyes containing stripes of sevenless+ and sevenless- ommatidia, suggesting that R7 cell fate can be specified only within a relatively short period during ommatidial assembly. These results support the hypothesis that the specification of cell fate by position depends on the interaction of a localized signal with a receptor present on many undifferentiated cells, and that the mere presence of the receptor alone is not sufficient to specify cell fate.  相似文献   

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Cross-regulatory interactions among pair-rule genes in Drosophila   总被引:14,自引:0,他引:14  
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蜜蜂是一种重要的授粉昆虫,也是研究人类疾病及社会行为的模式生物之一。由其基因组测序可知,蜜蜂基因组中(A+T)及CpG含量较高,其昼夜节律、RNAi和DNA甲基化基因更类似脊椎动物。先天免疫、表皮蛋白和味觉受体基因较少,气味受体基因较多。蜜蜂早期发育途径中的一些基因与果蝇的相似,功能却显著不同。本文综述了蜜蜂卵、幼虫、蛹和成虫期发育相关基因及其研究进展。  相似文献   

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Visual pigment homologies revealed by DNA hybridization   总被引:7,自引:0,他引:7  
A bovine rhodopsin complementary DNA probe was used to detect homologous visual pigment genes in a variety of species. Under stringent DNA hybridization conditions, genomic DNA from most vertebrate species carried a single homologous fragment. Additional homologies were detected in some vertebrates by reducing the hybridization stringency. Homologous fragments were also detected in DNA isolated from invertebrate species, a unicellular alga, and an archaebacterium; many of these fragments were homologous to a Drosophila opsin probe. These results suggest that photosensory pigments in a wide variety of species arose from a common precursor.  相似文献   

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A rat dopamine (DA) transporter complementary DNA has been isolated with combined complementary DNA homology and expression approaches. The DA transporter is a 619-amino acid protein with 12 hydrophobic putative membrane-spanning domains and homology to the norepinephrine and gamma-aminobutyric acid transporters. The expressed complementary DNA confers transport of [3H]DA in Xenopus oocytes and in COS cells. Binding of the cocaine analog [3H]CFT ([3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) to transfected COS cell membranes yields a pharmacological profile similar to that in striatal membranes.  相似文献   

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Soluble peptide factors have been implicated as the agents responsible for embryonic inductions in vertebrates. Here, a protein (PIF) secreted by a mouse macrophage cell line is shown to change the developmental fate of Xenopus embryonic cells. Exposure to PIF causes presumptive ectodermal explants to form anterior neural and mesodermal tissues, including brain and eye, instead of ciliated epidermis. In addition, the induced tissues are organized into a rudimentary embryonic axis. These results suggest that PIF or a closely related molecule is involved in inducing anterior structures and organizing the frog body plan.  相似文献   

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