Abstract:
:Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation of Rb and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. GFAP-Cre-mediated recombination was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. GFAP-Cre;Rb(LoxP/LoxP);p53(-/- or LoxP/LoxP) mice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Marino S,Vooijs M,van Der Gulden H,Jonkers J,Berns Asubject
Has Abstractpub_date
2000-04-15 00:00:00pages
994-1004issue
8eissn
0890-9369issn
1549-5477journal_volume
14pub_type
杂志文章abstract::Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environme...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.241182.114
更新日期:2014-04-15 00:00:00
abstract::Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.2.167
更新日期:1997-01-15 00:00:00
abstract::The Drosophila proteins Transformer (Tra) and Transformer2 (Tra2) regulate the sex-specific alternative splicing of Drosophila doublesex (dsx) pre-mRNA by specifically binding to a splicing enhancer (dsx repeat element; dsxRE) located 300 nucleotides (nt) downstream from a female-specific 3' splice site. In this paper...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.14.1703
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abstract::The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.24.3105
更新日期:1996-12-15 00:00:00
abstract::Signaling by the hormones brassinosteroid (BR) and gibberellin (GA) is critical to normal plant growth and development and is required for hypocotyl elongation in response to dark and elevated temperatures. Active BR signaling is essential for GA promotion of hypocotyl growth and suppresses the dwarf phenotype of GA m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.243675.114
更新日期:2014-08-01 00:00:00
abstract::Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathway...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.408407
更新日期:2007-03-01 00:00:00
abstract::MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.17221311
更新日期:2011-10-15 00:00:00
abstract::Covalent modifications of the histone N tails play important roles in eukaryotic gene expression. Histone acetylation, in particular, is required for the activation of a subset of eukaryotic genes through the targeted recruitment of histone acetyltransferases. We have reported that a histone C tail modification, ubiqu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1149604
更新日期:2004-01-15 00:00:00
abstract::To investigate the importance of sequences between the yeast (Saccharomyces cerevisiae) branch point (TACTAAC box) and 3' splice site (AG), we generated a series of pre-mRNA substrates that differed in the length of RNA retained on the 3' side of the TACTAAC box. These pre-mRNAs were compared as substrates for the fir...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.3.238
更新日期:1987-05-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1724308
更新日期:2008-11-15 00:00:00
abstract::A conditional allele of type 1 protein phosphatase (glc7-129) in Saccharomyces cerevisiae causes first cycle arrest in G2/M, characterized by cells with a short spindle and high H1 kinase activity. Point-of-execution experiments indicate Glc7p function is required in G2/M just before anaphase for the completion of mit...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.5.517
更新日期:1999-03-01 00:00:00
abstract::TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable som...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304972.117
更新日期:2017-09-15 00:00:00
abstract::Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.280941.116
更新日期:2016-05-15 00:00:00
abstract::During vasculogenesis and angiogenesis, endothelial cell responses to growth factors are modulated by the compositional and mechanical properties of a surrounding three-dimensional (3D) extracellular matrix (ECM) that is dominated by either cross-linked fibrin or type I collagen. While 3D-embedded endothelial cells es...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1643308
更新日期:2008-05-01 00:00:00
abstract::Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1827009
更新日期:2009-10-01 00:00:00
abstract::The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required for organogenesis. Targeted deletion of the COUP-TFII gene results in embryonic lethality with defects in angiogenesis and heart development. COUP-TFII mutants are defecti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.8.1037
更新日期:1999-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.15.2028
更新日期:1999-08-01 00:00:00
abstract::To understand the organization of the transcriptional networks that govern cell differentiation, we have investigated the transcriptional circuitry controlling pseudohyphal development in Saccharomyces cerevisiae. The binding targets of Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast geno...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1389306
更新日期:2006-02-15 00:00:00
abstract::Epigenetic modifications of chromatin play an important role in the regulation of gene expression. KMT4/Dot1 is a conserved histone methyltransferase capable of methylating chromatin on Lys79 of histone H3 (H3K79). Here we report the identification of a multisubunit Dot1 complex (DotCom), which includes several of the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1898410
更新日期:2010-03-15 00:00:00
abstract::The labial (lab) gene of Drosophila melanogaster is necessary for the proper development of the embryonic (larval) and adult head. We have identified the lab transcription unit within the proximal portion of the Antennapedia Complex (ANT-C) by mapping the molecular lesions associated with chromosomally rearranged lab ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.3.399
更新日期:1989-03-01 00:00:00
abstract::The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2006-07-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1439206
更新日期:2006-09-15 00:00:00
abstract::For all newborn mammals, mother's milk is the perfect nourishment, crucial for their postnatal development. Here we report that, unexpectedly, maternal western diet consumption in mice causes the production of toxic milk that contains excessive long chain and saturated fatty acids, which triggers ceramide accumulation...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.191031.112
更新日期:2012-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.248245.114
更新日期:2014-12-01 00:00:00
abstract::Transformation of primary rodent cells by the adenovirus E1A and E1B oncogenes is a two-step process, where E1A-dependent induction of proliferation is coupled to E1B-dependent suppression of programmed cell death (apoptosis). The E1B gene encodes two distinct transforming proteins, the 19K and 55K proteins, both of w...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.4.546
更新日期:1993-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.10.1233
更新日期:1996-05-15 00:00:00
abstract::Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potent...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.226837.113
更新日期:2013-11-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1415606
更新日期:2006-05-15 00:00:00
abstract::The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is require...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.312355.118
更新日期:2018-08-01 00:00:00
abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.18.2266
更新日期:1995-09-15 00:00:00