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  • 1
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    Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-06-06
    Description: Drosophila neuroblasts and ovarian stem cells are well characterized models for stem cell biology. In both cell types, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim-NHL (tripartite motif and Ncl-1, HT2A and Lin-41 domain)-containing protein Brain tumour (Brat) into one of the two daughter cells, ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit-amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim-NHL protein Mei-P26 (refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei-P26 expression is low in stem cells but is strongly induced in 16-cell cysts. In mei-P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute-1, a component of the RISC complex, as a common binding partner of Brat and Mei-P26, and show that Mei-P26 acts by inhibiting the microRNA pathway. Mei-P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988194/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988194/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neumuller, Ralph A -- Betschinger, Joerg -- Fischer, Anja -- Bushati, Natascha -- Poernbacher, Ingrid -- Mechtler, Karl -- Cohen, Stephen M -- Knoblich, Juergen A -- P 16629/Austrian Science Fund FWF/Austria -- England -- Nature. 2008 Jul 10;454(7201):241-5. doi: 10.1038/nature07014. Epub 2008 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18528333" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Cell Cycle ; Cell Differentiation ; Cell Enlargement ; Cell Line ; *Cell Lineage ; Cell Nucleolus/metabolism ; Cell Size ; DNA-Binding Proteins/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/classification/*cytology/genetics ; Eukaryotic Initiation Factors ; Female ; MicroRNAs/genetics/*metabolism ; Mutation ; Neurons/cytology/metabolism ; Ovary/*cytology/metabolism ; Stem Cells/*cytology/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-04-14
    Description: Genome-wide RNA interference (RNAi) screens have identified near-complete sets of genes involved in cellular processes. However, this methodology has not yet been used to study complex developmental processes in a tissue-specific manner. Here we report the use of a library of Drosophila strains expressing inducible hairpin RNAi constructs to study the Notch signalling pathway during external sensory organ development. We assigned putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes. Using secondary assays, we identified 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway. By integrating our phenotypic results with protein interaction data, we constructed a genome-wide, functionally validated interaction network governing Notch signalling and asymmetric cell division. We used clustering algorithms to identify nuclear import pathways and the COP9 signallosome as Notch regulators. Our results show that complex developmental processes can be analysed on a genome-wide level and provide a unique resource for functional annotation of the Drosophila genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988197/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988197/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mummery-Widmer, Jennifer L -- Yamazaki, Masakazu -- Stoeger, Thomas -- Novatchkova, Maria -- Bhalerao, Sheetal -- Chen, Doris -- Dietzl, Georg -- Dickson, Barry J -- Knoblich, Juergen A -- P 16629/Austrian Science Fund FWF/Austria -- England -- Nature. 2009 Apr 23;458(7241):987-92. doi: 10.1038/nature07936. Epub 2009 Apr 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19363474" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Animals, Genetically Modified ; Cell Division/genetics ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/*genetics/*metabolism ; Genome, Insect/*genetics ; Phenotype ; Quality Control ; *RNA Interference ; Receptors, Notch/*metabolism ; Signal Transduction/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-03-20
    Description: Endocytosis has a crucial role during Notch signalling after the asymmetric division of fly sensory organ precursors (SOPs): directional signalling is mediated by differential endocytosis of the ligand Delta and the Notch effector Sanpodo in one of the SOP daughters, pIIb. Here we show a new mechanism of directional signalling on the basis of the trafficking of Delta and Notch molecules already internalized in the SOP and subsequently targeted to the other daughter cell, pIIa. Internalized Delta and Notch traffic to an endosome marked by the protein Sara. During SOP mitosis, Sara endosomes containing Notch and Delta move to the central spindle and then to pIIa. Subsequently, in pIIa (but not in pIIb) Notch appears cleaved in Sara endosomes in a gamma-secretase- and Delta internalization-dependent manner, indicating that the release of the intracellular Notch tail to activate Notch target genes has occurred. We thus uncover a new mechanism to bias signalling even before asymmetric endocytosis of Sanpodo and Delta takes place in the daughter cells: already during SOP mitosis, asymmetric targeting of Delta and Notch-containing Sara endosomes will increase Notch signalling in pIIa and decrease it in pIIb.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coumailleau, F -- Furthauer, M -- Knoblich, J A -- Gonzalez-Gaitan, M -- England -- Nature. 2009 Apr 23;458(7241):1051-5. doi: 10.1038/nature07854. Epub 2009 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295516" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid Precursor Protein Secretases/metabolism ; Animal Structures/cytology/metabolism ; Animals ; Cell Differentiation ; Cell Division ; Cell Lineage ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/anatomy & histology/*cytology/genetics/*metabolism ; Endocytosis ; Endosomes/*metabolism ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins/*metabolism ; Mice ; Microfilament Proteins/metabolism ; Mitosis ; Protein Transport ; Receptors, Notch/*metabolism ; Signal Transduction ; Transforming Growth Factor beta/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Cell biology. Sara splits the signal (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knoblich, Juergen A -- New York, N.Y. -- Science. 2006 Nov 17;314(5802):1094-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria. juergen.knoblich@imba.oeaw.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17110561" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/*metabolism ; Endosomes/*metabolism ; Mitosis ; *Signal Transduction ; Smad Proteins, Receptor-Regulated/metabolism ; Transforming Growth Factor beta/*metabolism ; Wings, Animal/cytology/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Cerebral organoids model human brain development and microcephaly (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-09-03
    Description: The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817409/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817409/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lancaster, Madeline A -- Renner, Magdalena -- Martin, Carol-Anne -- Wenzel, Daniel -- Bicknell, Louise S -- Hurles, Matthew E -- Homfray, Tessa -- Penninger, Josef M -- Jackson, Andrew P -- Knoblich, Juergen A -- 250342/European Research Council/International -- I 552/Austrian Science Fund FWF/Austria -- MC_PC_U127580972/Medical Research Council/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Z 153/Austrian Science Fund FWF/Austria -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Sep 19;501(7467):373-9. doi: 10.1038/nature12517. Epub 2013 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna 1030, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23995685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/anatomy & histology/cytology/*growth & development/*pathology ; Cerebral Cortex/cytology/embryology/growth & development/pathology ; Humans ; Induced Pluripotent Stem Cells/cytology/pathology ; Mice ; Microcephaly/*pathology ; *Models, Biological ; Neural Stem Cells/cytology/pathology ; Neurogenesis ; Neurons/cytology/pathology ; Organoids/*cytology/embryology/*growth & development/pathology ; Tissue Culture Techniques/*methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Organogenesis in a dish: modeling development and disease using organoid technologies (2014)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2014-07-19
    Description: Classical experiments performed half a century ago demonstrated the immense self-organizing capacity of vertebrate cells. Even after complete dissociation, cells can reaggregate and reconstruct the original architecture of an organ. More recently, this outstanding feature was used to rebuild organ parts or even complete organs from tissue or embryonic stem cells. Such stem cell-derived three-dimensional cultures are called organoids. Because organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they have the potential to model human development and disease. Furthermore, they have potential for drug testing and even future organ replacement strategies. Here, we summarize this rapidly evolving field and outline the potential of organoid technology for future biomedical research.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lancaster, Madeline A -- Knoblich, Juergen A -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):1247125. doi: 10.1126/science.1247125. Epub 2014 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science Vienna 1030, Austria. ; IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science Vienna 1030, Austria. juergen.knoblich@imba.oeaw.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/physiology ; Cell Culture Techniques ; *Disease ; Drug Evaluation, Preclinical/methods ; Humans ; Intestines/physiology ; Liver/physiology ; Mice ; *Models, Biological ; Mutagenesis ; Organ Culture Techniques ; *Organogenesis ; Organoids/cytology/*growth & development ; Pluripotent Stem Cells/*cytology/physiology ; Retina/physiology ; Tissue Engineering
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    The Drosophila Numb protein inhibits signaling of the Notch receptor during cell-cell interaction in sensory organ lineage. (1996)
    National Academy of Sciences
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    Publication Date: 1996-10-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Analysis and modeling of mitotic spindle orientations in three dimensions (2013)
    National Academy of Sciences
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    Publication Date: 2013-12-31
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Cerebral organoids model neocortex gene networks [Developmental Biology] (2015)
    National Academy of Sciences
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    Publication Date: 2015-12-24
    Description: Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    The N terminus of the Drosophila Numb protein directs membrane association and actin-dependent asymmetric localization (1997)
    National Academy of Sciences
    Details
    Publication Date: 1997-11-25
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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