Genomes and Genes
Gene Symbol: insc
Alias: 25/17, CG11312, Dmel\CG11312, INSC, Ins, Insc, fam, l(2)05475, l(2)k12405, nem, inscuteable, CG11312-PA, fata morgana, insc-PA, inscrutable, inscutable, not enough muscles
Species: fruit fly
- Bellaiche Y, Radovic A, Woods D, Hough C, Parmentier M, O Kane C, et al. The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila. Cell. 2001;106:355-66 pubmed..The Discs-large (Dlg) and Partner of Inscuteable (Pins) proteins accumulate at the anterior cortex, while Bazooka (Baz) relocalizes to the posterior cortex...
- Siegrist S, Doe C. Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell. 2005;123:1323-35 pubmed..The microtubule/Khc-73/Dlg pathway acts in parallel to the well-characterized Inscuteable/Par pathway, but each provides unique spatial and temporal information: The Inscuteable/Par pathway initiates ..
- Emery G, Hutterer A, Berdnik D, Mayer B, Wirtz Peitz F, Gaitan M, et al. Asymmetric Rab 11 endosomes regulate delta recycling and specify cell fate in the Drosophila nervous system. Cell. 2005;122:763-73 pubmed..Our results suggest that cells can regulate signaling pathways and influence their developmental fate by inhibiting the formation of individual endocytic compartments...
- Buescher M, Yeo S, Udolph G, Zavortink M, Yang X, Tear G, et al. Binary sibling neuronal cell fate decisions in the Drosophila embryonic central nervous system are nonstochastic and require inscuteable-mediated asymmetry of ganglion mother cells. Genes Dev. 1998;12:1858-70 pubmed..The correct positioning of Numb and the proper orientation of division require Inscuteable (Insc). Loss of insc results in the generation of equivalent sibling cells...
- Wang H, Cai Y, Chia W, Yang X. Drosophila homologs of mammalian TNF/TNFR-related molecules regulate segregation of Miranda/Prospero in neuroblasts. EMBO J. 2006;25:5783-93 pubmed..In inscuteable mutant NBs, these basal proteins are mislocalized during metaphase...
- Tio M, Zavortink M, Yang X, Chia W. A functional analysis of inscuteable and its roles during Drosophila asymmetric cell divisions. J Cell Sci. 1999;112 ( Pt 10):1541-51 pubmed..so far which acts to organise both neuroblast and ganglion mother cell asymmetric divisions is encoded by inscuteable. The Inscuteable protein is itself asymmetrically localised to the apical cell cortex and is required both for ..
- Siegrist S, Doe C. Extrinsic cues orient the cell division axis in Drosophila embryonic neuroblasts. Development. 2006;133:529-36 pubmed..This ensures the proper coordination between neuroblast cell polarity and CNS tissue polarity. ..
- Kaltschmidt J, Davidson C, Brown N, Brand A. Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system. Nat Cell Biol. 2000;2:7-12 pubmed..This observation contradicts the widely held hypothesis that the cleavage furrow is always placed midway between the two centrosomes. ..
- Shen C, Knoblich J, Chan Y, Jiang M, Jan L, Jan Y. Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila. Genes Dev. 1998;12:1837-46 pubmed..The localization of Prospero requires the function of inscuteable and miranda, whereas prospero RNA localization requires inscuteable and staufen function...
- Doe C. Cell polarity: the PARty expands. Nat Cell Biol. 2001;3:E7-9 pubmed..This common cell-polarity mechanism is used in cell-specific ways, as highlighted by the recent finding that at least two different types of asymmetric division are observed in Drosophila neural precursors. ..
- Lu B, Rothenberg M, Jan L, Jan Y. Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors. Cell. 1998;95:225-35 pubmed..We propose that PON is one component of a multimolecular machinery that localizes Numb by responding to polarity cues conserved in neural precursors and epithelial cells. ..
- Yu F, Morin X, Cai Y, Yang X, Chia W. Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell. 2000;100:399-409 pubmedAsymmetric localization is a prerequisite for inscuteable (insc) to function in coordinating and mediating asymmetric cell divisions in Drosophila...
- Fuerstenberg S, Peng C, Alvarez Ortiz P, Hor T, Doe C. Identification of Miranda protein domains regulating asymmetric cortical localization, cargo binding, and cortical release. Mol Cell Neurosci. 1998;12:325-39 pubmed..Establishing neuroblast/GMC differences involves the asymmetric localization of proteins (Inscuteable, Miranda, Prospero, and Staufen) and RNA (prospero)...
- Petronczki M, Knoblich J. DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat Cell Biol. 2001;3:43-9 pubmed
- Kraut R, Chia W, Jan L, Jan Y, Knoblich J. Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Nature. 1996;383:50-5 pubmed..orientation of the mitotic spindle and correct localization of Numb and Prospero in these cells require the inscuteable gene. Moreover, ectopic expression of inscuteable in other epithelial cells leads to spindle reorientation...
- Ahringer J. Control of cell polarity and mitotic spindle positioning in animal cells. Curr Opin Cell Biol. 2003;15:73-81 pubmed..Microtubules and conserved PAR proteins are essential mediators of cell polarity, and mitotic spindle positioning depends on heterotrimeric G protein signalling and the microtubule motor protein dynein. ..
- Lu B, Roegiers F, Jan L, Jan Y. Adherens junctions inhibit asymmetric division in the Drosophila epithelium. Nature. 2001;409:522-5 pubmed..Our results indicate that neuroepithelial cells have all the necessary components to execute asymmetric division, but that this pathway is normally overridden by the planar polarity cue provided by adherens junctions. ..
- Cai Y, Yu F, Lin S, Chia W, Yang X. Apical complex genes control mitotic spindle geometry and relative size of daughter cells in Drosophila neuroblast and pI asymmetric divisions. Cell. 2003;112:51-62 pubmed..In sensory organ precursors, Bazooka/DaPKC and Pins/G alpha i localize to opposite sides of the cortex and function in opposition to generate a symmetric spindle. ..
- Schaefer M, Petronczki M, Dorner D, Forte M, Knoblich J. Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell. 2001;107:183-94 pubmed..Thus, asymmetric activation of heterotrimeric G proteins by a receptor-independent mechanism may orient asymmetric cell divisions in different cell types. ..
- Petritsch C, Tavosanis G, Turck C, Jan L, Jan Y. The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. Dev Cell. 2003;4:273-81 pubmed..In this process, apically localized Bazooka recruits Inscuteable and other proteins to form an apical complex, which then specifies spindle orientation and basal localization ..
- Schaefer M, Shevchenko A, Knoblich J. A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol. 2000;10:353-62 pubmedIn the fruit fly Drosophila, the Inscuteable protein localises to the apical cell cortex in neuroblasts and directs both the apical-basal orientation of the mitotic spindle and the basal localisation of the protein determinants Numb and ..
- Egger B, Boone J, Stevens N, Brand A, Doe C. Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe. Neural Dev. 2007;2:1 pubmed..neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation...
- Doe C, Bowerman B. Asymmetric cell division: fly neuroblast meets worm zygote. Curr Opin Cell Biol. 2001;13:68-75 pubmed..Mammalian epithelia also use this complex to regulate apical/basal polarity. Recent results have allowed us to compare the mechanisms regulating asymmetric cell division in Drosophila neuroblasts and the C. elegans zygote. ..
- Wirtz Peitz F, Nishimura T, Knoblich J. Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell. 2008;135:161-73 pubmed publisher..Our data reveal a molecular mechanism for the asymmetric localization of Numb and show how cell polarity can be coupled to cell-cycle progression. ..
- Schober M, Schaefer M, Knoblich J. Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts. Nature. 1999;402:548-51 pubmed..of the mitotic spindle and the localization of Numb and Miranda to the basal cell cortex are directed by Inscuteable, a protein that localizes to the apical cell cortex before and during neuroblast mitosis...
- Betschinger J, Knoblich J. Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Curr Biol. 2004;14:R674-85 pubmed..Here, we outline the steps and factors that are involved in this process in Drosophila and C. elegans and discuss their potential conservation in vertebrates. ..
- Cai Y, Chia W, Yang X. A family of snail-related zinc finger proteins regulates two distinct and parallel mechanisms that mediate Drosophila neuroblast asymmetric divisions. EMBO J. 2001;20:1704-14 pubmed..We show that simultaneous removal of all three genes causes defective neuroblast asymmetric divisions; inscuteable transcription/translation is delayed/suppressed in the segmented CNS...
- Lu B, Ackerman L, Jan L, Jan Y. Modes of protein movement that lead to the asymmetric localization of partner of Numb during Drosophila neuroblast division. Mol Cell. 1999;4:883-91 pubmed..This movement can occur when myosin motor activity is inhibited. However, the restriction of Pon to the basal cortex requires both actomyosin and Inscuteable.
- Li P, Yang X, Wasser M, Cai Y, Chia W. Inscuteable and Staufen mediate asymmetric localization and segregation of prospero RNA during Drosophila neuroblast cell divisions. Cell. 1997;90:437-47 pubmedWhen neuroblasts divide, inscuteable acts to coordinate protein localization and mitotic spindle orientation, ensuring that asymmetrically localized determinants like Prospero partition into one progeny...
- Albertson R, Doe C. Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nat Cell Biol. 2003;5:166-70 pubmed..We conclude that Dlg/Scrib/Lgl are important in regulating cortical polarity, cell size asymmetry and mitotic spindle asymmetry in Drosophila neuroblasts. ..
- Huttner W, Brand M. Asymmetric division and polarity of neuroepithelial cells. Curr Opin Neurobiol. 1997;7:29-39 pubmed
- Kaltschmidt J, Brand A. Asymmetric cell division: microtubule dynamics and spindle asymmetry. J Cell Sci. 2002;115:2257-64 pubmed..In this commentary we discuss recent findings on how the mitotic spindle is positioned and on cleavage site induction and place them in the context of cell size asymmetry in different model organisms. ..
- Speicher S, Fischer A, Knoblich J, Carmena A. The PDZ protein Canoe regulates the asymmetric division of Drosophila neuroblasts and muscle progenitors. Curr Biol. 2008;18:831-7 pubmed publisher..Here, we show that Cno functions as a new effector of the apical proteins Inscuteable (Insc)-Partner of Inscuteable (Pins)-Galphai during the asymmetric division of Drosophila neuroblasts (NBs)...
- Matsuzaki F. Asymmetric division of Drosophila neural stem cells: a basis for neural diversity. Curr Opin Neurobiol. 2000;10:38-44 pubmed..Our understanding now extends to the molecular nature of the cell polarity that underlies asymmetric divisions. This polarity is conserved among neural stem cells, epithelial cells and fertilized eggs. ..
- Rolls M, Albertson R, Shih H, Lee C, Doe C. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol. 2003;163:1089-98 pubmed..and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation...
- Shen C, Jan L, Jan Y. Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell. 1997;90:449-58 pubmed..The asymmetric localization of Miranda protein requires inscuteable. Our results suggest that miranda functions downstream of inscuteable and works as an adapter that connects ..
- Cayouette M, Raff M. Asymmetric segregation of Numb: a mechanism for neural specification from Drosophila to mammals. Nat Neurosci. 2002;5:1265-9 pubmed..Here, we review these and other findings that suggest an important role for the asymmetric segregation of Numb proteins in vertebrate neural development. ..
- Tio M, Udolph G, Yang X, Chia W. cdc2 links the Drosophila cell cycle and asymmetric division machineries. Nature. 2001;409:1063-7 pubmed..In Drosophila neural progenitors, Inscuteable, Partner of Inscuteable and Bazooka localize as an apical cortical complex at interphase, which directs the ..
- Sousa Nunes R, Chia W, Somers W. Protein phosphatase 4 mediates localization of the Miranda complex during Drosophila neuroblast asymmetric divisions. Genes Dev. 2009;23:359-72 pubmed publisher..Our findings suggest that Flfl may target PP4 to the MIra protein complex to facilitate dephosphorylation step(s) crucial for its cortical association/asymmetric localization. ..
- Wodarz A, Ramrath A, Kuchinke U, Knust E. Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Nature. 1999;402:544-7 pubmed..In Drosophila neuroblasts, inscuteable controls both spindle orientation and the asymmetric localization of the cell-fate determinants Prospero and ..
- Betschinger J, Mechtler K, Knoblich J. Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell. 2006;124:1241-53 pubmed..Similar defects are seen in lethal giant larvae (lgl) mutants where Brat and Prospero are not asymmetric. We have identified a molecular mechanism that may control self-renewal and prevent tumor formation in other stem cells as well. ..
- Kraut R, Campos Ortega J. inscuteable, a neural precursor gene of Drosophila, encodes a candidate for a cytoskeleton adaptor protein. Dev Biol. 1996;174:65-81 pubmed..We have isolated and characterized a novel neural precursor gene, inscuteable, whose expression is coincident with sites of cell shape changes or cell and tissue movement in the embryo, e.g...
- Chia W, Yang X. Asymmetric division of Drosophila neural progenitors. Curr Opin Genet Dev. 2002;12:459-64 pubmed..Recent findings also suggest possible mechanisms by which the processes of cell-cycle progression, neuronal lineage development and asymmetric divisions may be integrated. ..
- Yu F, Wang H, Qian H, Kaushik R, Bownes M, Yang X, et al. Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes Dev. 2005;19:1341-53 pubmed..Thus, Loco can potentially regulate heterotrimeric G-protein signaling via two distinct modes of action during Drosophila neuroblast asymmetric divisions. ..
- Izumi Y, Ohta N, Hisata K, Raabe T, Matsuzaki F. Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nat Cell Biol. 2006;8:586-93 pubmed..We propose that Drosophila Mud, vertebrate NuMA and Caenorhabditis elegans Lin-5 (refs 5, 6) have conserved roles in the mechanism by which G-proteins regulate the mitotic spindle. ..
- Nipper R, Siller K, Smith N, Doe C, Prehoda K. Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts. Proc Natl Acad Sci U S A. 2007;104:14306-11 pubmed..We conclude that Pins has multiple activity states that generate cortical polarity and link it with mitotic spindle orientation. ..
- Ceron J, Gonzalez C, Tejedor F. Patterns of cell division and expression of asymmetric cell fate determinants in postembryonic neuroblast lineages of Drosophila. Dev Biol. 2001;230:125-38 pubmed..iii) This change in the pattern of division correlates with the expression of inscuteable, which is apically localized only in asymmetric divisions...
- Peng C, Manning L, Albertson R, Doe C. The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature. 2000;408:596-600 pubmed..We conclude that Dlg and Lgl promote, and myosin II inhibits, actomyosin-dependent basal protein targeting in neuroblasts. ..
- Wodarz A, Ramrath A, Grimm A, Knust E. Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol. 2000;150:1361-74 pubmed..In the latter, Baz anchors Inscuteable in the apical cytocortex, which is essential for asymmetric localization of cell fate determinants and for ..
- Knirr S, Breuer S, Paululat A, Renkawitz Pohl R. Somatic mesoderm differentiation and the development of a subset of pericardial cells depend on the not enough muscles (nem) locus, which contains the inscuteable gene and the intron located gene, skittles. Mech Dev. 1997;67:69-81 pubmedb>Not enough muscles (nem) mutants of Drosophila reveal defects in the development of embryonic muscles, a subset of pericardial cells, the CNS and derivatives of the PNS (Burchard, S., Paululat, A., Hinz, U. and Renkawitz-Pohl, R...
- Lee C, Andersen R, Cabernard C, Manning L, Tran K, Lanskey M, et al. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev. 2006;20:3464-74 pubmed..We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal. ..
- Jan Y, Jan L. Asymmetric cell division. Nature. 1998;392:775-8 pubmed
- Burchard S, Paululat A, Hinz U, Renkawitz Pohl R. The mutant not enough muscles (nem) reveals reduction of the Drosophila embryonic muscle pattern. J Cell Sci. 1995;108 ( Pt 4):1443-54 pubmed..development in Drosophila we identified a mutation caused by the insertion of a P-element, which we called not enough muscles (nem)...
- Akong K, McCartney B, Peifer M. Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations. Dev Biol. 2002;250:71-90 pubmed..Our experiments suggest that this does not result from misregulation of Wg signaling, and thus may involve the cytoskeletal or adhesive roles of APC proteins. ..
- Irion U, Leptin M. Developmental and cell biological functions of the Drosophila DEAD-box protein abstrakt. Curr Biol. 1999;9:1373-81 pubmed..Abstrakt must affect processing of specific subsets of RNAs, suggesting that differential post-translational control during development is more common than previously suspected. ..
- Tuxworth R, Chia W. Asymmetric cell division: Miranda chauffeured by Jaguar?. Mol Cell. 2003;11:288-9 pubmed..An intact F-actin cytoskeleton was known to be required, and now a myosin VI (Jaguar) has been shown to be necessary for basal targeting of cell fate determinants in neuroblasts. ..
- Sellin J, Drechsler M, Nguyen H, Paululat A. Antagonistic function of Lmd and Zfh1 fine tunes cell fate decisions in the Twi and Tin positive mesoderm of Drosophila melanogaster. Dev Biol. 2009;326:444-55 pubmed publisher..We show further that Tin repression and pericardial restriction in the dorsal mesoderm facilitated by Lmd is instructed by a late Decapentaplegic (Dpp) signal that is abolished in embryos carrying the disk region mutation dpp(d6). ..