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Yuh Nung Jan - One of the best experts on this subject based on the ideXlab platform.
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lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the drosophila adult Sensory Organ precursor lineage
Current Biology, 2003Co-Authors: Nicholas J Justice, Fabrice Roegiers, Lily Yeh Jan, Yuh Nung JanAbstract:The tumor suppressor genes lethal giant larvae (lgl) and discs large (dlg) act together to maintain the apical basal polarity of epithelial cells in the Drosophila embryo. Neuroblasts that delaminate from the embryonic epithelium require lgl to promote formation of a basal Numb and Prospero crescent, which will be asymmetrically segregated to the basal daughter cell upon division to specify cell fate. Sensory Organ precursors (SOPs) also segregate Numb asymmetrically at cell division. Numb functions to inhibit Notch signaling and to specify the fates of progenies of the SOP that constitute the cellular components of the adult Sensory Organ. We report here that, in contrast to the embryonic neuroblast, lgl is not required for asymmetric localization of Numb in the dividing SOP. Nevertheless, mosaic analysis reveals that lgl is required for cell fate specification within the SOP lineage; SOPs lacking Lgl fail to specify internal neurons and glia. Epistasis studies suggest that Lgl acts to inhibit Notch signaling by functioning downstream or in parallel with Numb. These findings uncover a previously unknown function of Lgl in the inhibition of Notch and reveal different modes of action by which Lgl can influence cell fate in the neuroblast and SOP lineages.
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bazooka is required for localization of determinants and controlling proliferation in the Sensory Organ precursor cell lineage in drosophila
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Fabrice Roegiers, Lily Yeh Jan, Susan Youngershepherd, Yuh Nung JanAbstract:Asymmetric divisions with two different division orientations follow different polarity cues for the asymmetric segregation of determinants in the Sensory Organ precursor (SOP) lineage. The first asymmetric division depends on frizzled function and has the mitotic spindle of the pI cell in the epithelium oriented along the anterior–posterior axis, giving rise to pIIa and pIIb, which divide in different orientations. Only the pIIb division resembles neuroblast division in daughter-size asymmetry, spindle orientation along the apical–basal axis, basal Numb localization, and requirement for inscuteable function. Because the PDZ domain protein Bazooka is required for spindle orientation and basal localization of Numb in neuroblasts, we wondered whether Bazooka plays a similar role in the pIIb in the SOP lineage. Surprisingly, Bazooka controls asymmetric localization of the Numb-anchoring protein Pon, but not spindle orientation, in pI and all subsequent divisions. Bazooka also regulates cell proliferation in the SOP lineage; loss of bazooka function results in supernumerary cell divisions and apoptotic cell death.
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two types of asymmetric divisions in the drosophila Sensory Organ precursor cell lineage
Nature Cell Biology, 2001Co-Authors: Fabrice Roegiers, Lily Yeh Jan, Susan Youngershepherd, Yuh Nung JanAbstract:Asymmetric partitioning of cell-fate determinants during development requires coordinating the positioning of these determinants with orientation of the mitotic spindle. In the Drosophila peripheral nervous system, Sensory Organ progenitor cells (SOPs) undergo several rounds of division to produce five cells that give rise to a complete Sensory Organ. Here we have observed the asymmetric divisions that give rise to these cells in the developing pupae using green fluorescent protein fusion proteins. We find that spindle orientation and determinant localization are tightly coordinated at each division. Furthermore, we find that two types of asymmetric divisions exist within the Sensory Organ precursor cell lineage: the anterior-posterior pI cell-type division, where the spindle remains symmetric throughout mitosis, and the strikingly neuroblast-like apical-basal division of the pIIb cell, where the spindle exhibits a strong asymmetry at anaphase. In both these divisions, the spindle reorientates to position itself perpendicular to the region of the cortex containing the determinant. On the basis of these observations, we propose that two distinct mechanisms for controlling asymmetric cell divisions occur within the same lineage in the developing peripheral nervous system in Drosophila.
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a gain of function screen for genes that affect the development of the drosophila adult external Sensory Organ
Genetics, 2000Co-Authors: Salim Abdelilahseyfried, Lily Yeh Jan, Susan Youngershepherd, Yeeming Chan, Chaoyang Zeng, Nicholas J Justice, Linda Sharp, Sandra Barbel, Sarah Meadows, Yuh Nung JanAbstract:The Drosophila adult external Sensory Organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in Sensory Organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rorth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external Sensory Organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external Sensory Organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external Sensory Organs or subsets of Sensory Organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system.
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flamingo controls the planar polarity of Sensory bristles and asymmetric division of Sensory Organ precursors in drosophila
Current Biology, 1999Co-Authors: Tadao Usui, Tadashi Uemura, Lily Yeh Jan, Yuh Nung JanAbstract:Abstract The Sensory bristles of the fruit fly Drosophila are Organized in a polarized fashion such that bristles on the thorax point posteriorly. These bristles are derived from asymmetric division of Sensory Organ precursors (SOPs). The Numb protein, which is localized asymmetrically in a cortical crescent in each SOP, segregates into only one of the two daughter cells during cell division, thereby conferring distinct fates to the daughter cells [1,2]. In neuroblasts, establishment of apical–basal polarity by the protein Inscuteable is crucial for orienting asymmetric division, but this is not the case for division of SOPs [3]. Instead, the Frizzled (Fz) protein mediates a planar polarity signal that controls the anteroposteriorly oriented first division (pl) of SOPs [4]. Here, we report that Flamingo (Fmi), a seven-transmembrane cadherin [5], controls the planar polarity of Sensory bristles and the orientation of the SOP pl division. Both the loss of function and overexpression of fmi disrupted bristle polarity. During mitosis of the SOP, the axis of the pl division and the positioning of the Numb crescent were randomized in the absence of Fmi activity. Overexpression of Fmi and Fz caused similar effects. The dependence of proper Fmi localization on Fz activity suggests that Fmi functions downstream of Fz in controlling planar polarity. We also present evidence suggesting that Fz also functions in the Wingless pathway to pattern Sensory Organs.
Francois Schweisguth - One of the best experts on this subject based on the ideXlab platform.
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intra lineage fate decisions involve activation of notch receptors basal to the midbody in drosophila Sensory Organ precursor cells
Current Biology, 2017Co-Authors: Francois Schweisguth, Khalil Mazouni, Mateusz TrylinskiAbstract:Summary Notch receptors regulate cell fate decisions during embryogenesis and throughout adult life. In many cell lineages, binary fate decisions are mediated by directional Notch signaling between the two sister cells produced by cell division. How Notch signaling is restricted to sister cells after division to regulate intra-lineage decision is poorly understood. More generally, where ligand-dependent activation of Notch occurs at the cell surface is not known, as methods to detect receptor activation in vivo are lacking. In Drosophila pupae, Notch signals during cytokinesis to regulate the intra-lineage pIIa/pIIb decision in the Sensory Organ lineage. Here, we identify two pools of Notch along the pIIa-pIIb interface, apical and basal to the midbody. Analysis of the dynamics of Notch, Delta, and Neuralized distribution in living pupae suggests that ligand endocytosis and receptor activation occur basal to the midbody. Using selective photo-bleaching of GFP-tagged Notch and photo-tracking of photo-convertible Notch, we show that nuclear Notch is indeed produced by receptors located basal to the midbody. Thus, only a specific subset of receptors, located basal to the midbody, contributes to signaling in pIIa. This is the first in vivo characterization of the pool of Notch contributing to signaling. We propose a simple mechanism of cell fate decision based on intra-lineage signaling: ligands and receptors localize during cytokinesis to the new cell-cell interface, thereby ensuring signaling between sister cells, hence intra-lineage fate decision.
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Self-Organized Notch dynamics generate stereotyped Sensory Organ patterns in Drosophila
Science, 2017Co-Authors: Francis Corson, Khalil Mazouni, Lydie Couturier, Hervé Rouault, Francois SchweisguthAbstract:INTRODUCTION: Spatial patterning in developing multicellular Organisms relies on positional cues and cell-cell interactions. Stereotyped Sensory Organ arrangements in Drosophila are commonly attributed to a prepattern that defines regions of neural competence. Notch-mediated interactions then isolate Sensory Organ precursor (SOP) cells from among the competent cells. In support of this view, prepattern factors direct the expression of proneural factors in discrete clusters and determine the location of large bristles on the dorsal thorax. However, no such prepattern is known to establish the proneural stripes that give rise to finer-bristle rows. RATIONALE: By analogy with reaction-diffusion systems, we wondered whether Notch-mediated cell-cell interactions might Organize a pattern of proneural stripes. To explore a possible role for Notch in proneural patterning, we generated fluorescent reporters for the proneural factors Achaete and Scute, the ligand Delta, and the Notch early-response factor E(spl)m3-HLH, which antagonizes proneural activity. We observed expression of these reporters in live and fixed samples throughout early pupal development. In parallel, we developed a mathematical model for Notch-mediated patterning. In this abstract model, the dynamics of a cell is expressed in terms of just two variables, for the state of the cell and the level of signal it receives. The model incorporates a series of plausible assumptions that govern its patterning behavior: Cells, which adopt the SOP fate in the absence of signal and the alternative, epidermal fate under high enough signal, exhibit a bistable response under intermediate signal levels. Inhibitory signaling from a cell varies nonlinearly with cell state and reaches beyond immediate neighbors. RESULTS: Before the onset of proneural gene expression, a bimodal gradient of Delta expression drove Notch activity; as a result of cis-inhibition, Notch was activated only in regions of intermediate Delta levels. This defined an inhibitory template for a first series of three proneural stripes. The spatial pattern of Notch activity dynamically changed as these first proneural stripes emerged, forming a negative template for a second group of intercalating stripes. Eventually, each stripe resolved into a row of isolated SOPs through Notch signaling. Thus, Notch mediated both proneural stripe patterning and SOP selection via a self-Organized process. Simulations of the model, with a time-dependent inhibitory gradient describing the proneural-independent signaling seen in vivo, recapitulated the sequential emergence and resolution of proneural stripes. In both model and experiments, mutual inhibition drove a gradual refinement of the proneural group, concomitant with the buildup of proneural activity. Cells on the sides of the stripes were excluded first, such that stripes narrowed before isolated SOPs emerged. In terms of the model, cell-intrinsic bistability allowed cells with higher proneural activity, at the center of the stripes, to evade levels of inhibition that were sufficient to exclude cells on the sides. Nonlinear signaling allowed a smooth transition from weak mutual inhibition within an extended proneural group to strong lateral inhibition from emerging SOPs, ensuring that attrition of the proneural group proceeds until only isolated cells remain. Finally, the model correctly predicted the outcome of perturbation experiments affecting the pattern of Notch activity, the level and activity of Delta, and the range of signaling. CONCLUSION:Our results show that self-Organized Notch signaling can establish stripe and dot patterns on a tissue-wide scale. A transient spatial bias, mediated by an initial gradient of Delta, is transduced by cell-cell interactions to produce a finer pattern of proneural stripes and bristle rows. Input from extrinsic positional cues and self-Organization, sometimes considered competing paradigms for fate patterning, combine during bristle development and operate through the same signal. Self-Organized Notch dynamics may provide a flexible substrate to generate diverse patterns in response to varying inputs.
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Regulation of cortical stability by RhoGEF3 in mitotic Sensory Organ Precursor cells in Drosophila
Biology Open, 2017Co-Authors: Lydie Couturier, Khalil Mazouni, Fred Bernard, Charlotte Besson, Elodie Reynaud, Francois SchweisguthAbstract:In epithelia, mitotic cells round up and push against their neighbors to divide. Mitotic rounding results from increased assembly of F-actin and cortical recruitment of Myosin II, leading to increased cortical stability. Whether this process is developmentally regulated is not well known. Here, we examined the regulation of cortical stability in Sensory Organ Precursor cells (SOPs) in the Drosophila pupal notum. SOPs differed in apical shape and actomyosin dynamics from their epidermal neighbors prior to division, and appeared to have a more rigid cortex at mitosis. We identified RhoGEF3 as an actin regulator expressed at higher levels in SOPs, and showed that RhoGEF3 had in vitro GTPase Exchange Factor (GEF) activity for Cdc42. Additionally, RhoGEF3 genetically interacted with both Cdc42 and Rac1 when overexpressed in the fly eye. Using a null RhoGEF3 mutation generated by CRISPR-mediated homologous recombination, we showed using live imaging that the RhoGEF3 gene, despite being dispensable for normal development, contributed to cortical stability in dividing SOPs. We therefore suggest that cortical stability is developmentally regulated in dividing SOPs of the fly notum.
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asymmetric cell division in the drosophila bristle lineage from the polarization of Sensory Organ precursor cells to notch mediated binary fate decision
Wiley Interdisciplinary Reviews-Developmental Biology, 2015Co-Authors: Francois SchweisguthAbstract:Asymmetric cell division (ACD) is a simple and evolutionary conserved process whereby a mother divides to generate two daughter cells with distinct developmental potentials. This process can generate cell fate diversity during development. Fate asymmetry may result from the unequal segregation of molecules and/or Organelles between the two daughter cells. Here, I will review how fate asymmetry is regulated in the Sensory bristle lineage in Drosophila and focus on the molecular mechanisms underlying ACD of the Sensory Organ precursor cells (SOPs). WIREs Dev Biol 2015, 4:299–309. doi: 10.1002/wdev.175 For further resources related to this article, please visit the WIREs website. Conflict of interest: The author has declared no conflicts of interest for this article.
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Overexpression of partner of numb induces asymmetric distribution of the PI4P 5-Kinase Skittles in mitotic Sensory Organ precursor cells in Drosophila.
PLoS ONE, 2008Co-Authors: Carolina N L R Perdigoto, Erin Overstreet, Janice Fischer, Antoine Guichet, Louis Gervais, Francois SchweisguthAbstract:Unequal segregation of cell fate determinants at mitosis is a conserved mechanism whereby cell fate diversity can be generated during development. In Drosophila, each Sensory Organ precursor cell (SOP) divides asymmetrically to produce an anterior pIIb and a posterior pIIa cell. The Par6-aPKC complex localizes at the posterior pole of dividing SOPs and directs the actin-dependent localization of the cell fate determinants Numb, Partner of Numb (Pon) and Neuralized at the opposite pole. The plasma membrane lipid phosphatidylinositol (4,5)-bisphosphate (PIP2) regulates the plasma membrane localization and activity of various proteins, including several actin regulators, thereby modulating actin-based processes. Here, we have examined the distribution of PIP2 and of the PIP2-producing kinase Skittles (Sktl) in mitotic SOPs. Our analysis indicates that both Sktl and PIP2 reporters are uniformly distributed in mitotic SOPs. In the course of this study, we have observed that overexpression of full-length Pon or its localization domain (LD) fused to the Red Fluorescent Protein (RFP::Pon(LD)) results in asymmetric distribution of Sktl and PIP2 reporters in dividing SOPs. Our observation that Pon overexpression alters polar protein distribution is relevant because RFP::Pon(LD) is often used as a polarity marker in dividing progenitors.
James W Posakony - One of the best experts on this subject based on the ideXlab platform.
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gain of function alleles of bearded interfere with alternative cell fate decisions in drosophila adult Sensory Organ development
Developmental Biology, 1996Co-Authors: Michael W Leviten, James W PosakonyAbstract:We have isolated a novel class of gain-of-function mutations at the Bearded (Brd) locus which specifically affect the development of adult Sensory Organs in Drosophila. These Brd alleles cause bristle multiplication and bristle loss phenotypes resembling those described for the neurogenic genes Notch (N) and Delta (Dl). We have found that supernumerary Sensory Organ precursor (SOP) cells develop in the proneural clusters of Brd mutant imaginal discs; like normal SOPs, these are dependent on the function of the proneural genes achaete and scute, and express elevated levels of ac protein. At cuticular positions exhibiting the Brd bristle loss phenotype, we have found that the progeny of the multiplied SOPs develop aberrantly, in that neurons and thecogen (sheath) cells appear but not trichogen (shaft) and tormogen (socket) cells. This appears to represent a transformation of the pIIa secondary precursor cell within the SOP lineage to a pIIb secondary precursor cell fate. These results suggest that Brd gain-of-function alleles interfere with Notch pathway-dependent cell ‐cell interactions at two distinct stages of adult Sensory Organ development. We have also identified enhancers and suppressors of the Brd dominant phenotypes; these include both previously characterized mutations and alleles of apparently novel loci. Finally, we have found that Brd null mutants are viable and exhibit no mutant phenotypes, suggesting that Brd may be a component of an overlapping function. q 1996 Academic Press, Inc.
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hairlesspromotes stable commitment to the Sensory Organ precursor cell fate by negatively regulating the activity of thenotchsignaling pathway
Developmental Biology, 1995Co-Authors: Anne G Bang, Adina M Bailey, James W PosakonyAbstract:Abstract InDrosophilaimaginal discs, the function of theHairless(H) gene is required at multiple steps during the development of adult Sensory Organs. Here we report the results of a series of experiments designed to investigate thein vivorole ofHin Sensory Organ precursor (SOP) cell specification. We show that the proneural cluster pattern of proneural gene expression and of transcriptional activation by proneural proteins is established normally in the absence ofHactivity. By contrast, single cells with the high levels ofachaete, scabrous,andneuralizedexpression characteristic of SOPs almost always fail to appear inHmutant proneural clusters. These results indicate thatHis required for a relatively late step in the development of the proneural cluster, namely, the stable commitment of a single cell to the SOP cell fate. We also show that expression of an activated form of the Notch receptor leads to bristle loss with the same cellular basis—failure of SOP determination—as loss ofHfunction and that simultaneous overexpression ofHsuppresses this effect. Finally, we demonstrate by epistasis experiments that the failure of stable commitment to the SOP fate inHnull mutants requires the activity of the genes of theEnhancer of splitcomplex, includinggroucho.Our results indicate thatHpromotes SOP determination by antagonizing the activity of theNotchpathway in this cell, thereby protecting it from inhibitory signaling by its neighbors in the proneural cluster. We propose a simple threshold model in which the principal role ofHin SOP specification is to translate a quantitative difference in the activity of theNotchpathway (in the SOP versus the non-SOP cells) into a stable binary cell fate decision.
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the drosophila gene hairless encodes a novel basic protein that controls alternative cell fates in adult Sensory Organ development
Genes & Development, 1992Co-Authors: Anne G Bang, James W PosakonyAbstract:The mechanoSensory bristles of adult Drosophila are composed of four cells that, in most cases, are progeny of a single Sensory Organ precursor (SOP) cell. Two sister cells in this lineage, the trichogen and tormogen, produce the external shaft and socket of the bristle, respectively. Loss-of-function mutations of Hairless (H) confer two distinct mutant phenotypes on adult bristles. The bristle loss phenotype results from the failure to specify and/or execute the SOP cell fate; the double socket phenotype results from the transformation of the trichogen (shaft) cell into a second tormogen (socket) cell. We have found that the H gene encodes a novel basic protein with a predicted molecular mass of 109 kD. Basal levels of expression of a transgene (P[Hs-H]) in which the H protein-coding region is under the control of the Hsp70 promoter are sufficient to provide full rescue of H mutant phenotypes. Heat shock treatment of P[Hs-H] transgenic animals as late larvae and early pupae produces a tormogen-to-trichogen (double shaft) cell fate transformation, as well as bristle multiplication and loss phenotypes very similar to those caused by loss-of-function mutations in the neurogenic gene Notch. Our results indicate that the SOP cell fate requires H to antagonize the activity of the neurogenic group of genes and that the expression of distinct cell fates by the trichogen/tormogen sister cell pair depends on an asymmetry in their levels of H ÷ activity or in their thresholds for response to H.
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suppressor of hairless the drosophila homolog of the mouse recombination signal binding protein gene controls Sensory Organ cell fates
Cell, 1992Co-Authors: Francois Schweisguth, James W PosakonyAbstract:Abstract Suppressor of Hairless (Su(H)) is required at two stages of adult Sensory Organ development in Drosophila. Complete loss of Su(H) function results in a "neurogenic" phenotype in imaginal discs, in which too many cells adopt the Sensory Organ precursor cell fate. Su(H) is also involved in controlling the fates of sensillum accessory cells and is specifically expressed in two of these cells. Su(H) is the Drosophila homolog of the mouse J κ RBP gene, whose product binds specifically to the recombination signal sequence of immunoglobulin J κ segments. The SU(H) and J κ RBP proteins are 82% identical over most of their length, and share with bacteriophage integrases and yeast recombinases a motif that includes residues directly involved in catalyzing recombination.
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hairless is required for the development of adult Sensory Organ precursor cells in drosophila
Development, 1991Co-Authors: Anne G Bang, Volker Hartenstein, James W PosakonyAbstract:Reduction of the wild-type activity of the gene Hairless (H) results in two major phenotypic effects on the mechanoSensory bristles of adult Drosophila. Bristles are either ‘lost’ (i.e. the shaft and socket fail to appear) or they exhibit a ‘double socket’ phenotype, in which the shaft is apparently transformed into a second socket. Analysis of the phenotypes conferred by a series of H mutant genotypes demonstrates (1) that different sensilla exhibit different patterns of response to decreasing levels of H+ function, and (2) that the ‘bristle loss’ phenotype results from greater loss of H+ function than the ‘double socket’ phenotype. The systematic study of H allelic combinations enabled us to identify genotypes that reliably produce specific mutant defects in particular positions on the bodies of adult flies. This permitted us to investigate the cellular development of sensilla in these same positions in larvae and pupae and thereby establish the developmental basis for the mutant phenotypes. We have found that H is required for at least two steps of adult sensillum development. In positions where ‘double socket’ microchaetes appear on the notum of H mutant flies, sensillum precursor cells are present in the developing pupa and divide normally, but their progeny adopt an aberrant spatial arrangement and fail to differentiate correctly. In regions of the notum exhibiting ‘bristle loss’ in adult H mutants, we were unable at the appropriate stages of development to detect sensillum-specific cell types, the precursor cell divisions that generate them, or the primary precursor cells themselves. Thus, the H ‘bristle loss’ phenotype appears to reflect a very early defect in sensillum development, namely the failure to specify and/or execute the Sensory Organ precursor cell fate. This finding indicates that H is one of a small number of identified genes for which the loss-of-function phenotype is the failure of sensillum precursor cell development.
Lily Yeh Jan - One of the best experts on this subject based on the ideXlab platform.
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lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the drosophila adult Sensory Organ precursor lineage
Current Biology, 2003Co-Authors: Nicholas J Justice, Fabrice Roegiers, Lily Yeh Jan, Yuh Nung JanAbstract:The tumor suppressor genes lethal giant larvae (lgl) and discs large (dlg) act together to maintain the apical basal polarity of epithelial cells in the Drosophila embryo. Neuroblasts that delaminate from the embryonic epithelium require lgl to promote formation of a basal Numb and Prospero crescent, which will be asymmetrically segregated to the basal daughter cell upon division to specify cell fate. Sensory Organ precursors (SOPs) also segregate Numb asymmetrically at cell division. Numb functions to inhibit Notch signaling and to specify the fates of progenies of the SOP that constitute the cellular components of the adult Sensory Organ. We report here that, in contrast to the embryonic neuroblast, lgl is not required for asymmetric localization of Numb in the dividing SOP. Nevertheless, mosaic analysis reveals that lgl is required for cell fate specification within the SOP lineage; SOPs lacking Lgl fail to specify internal neurons and glia. Epistasis studies suggest that Lgl acts to inhibit Notch signaling by functioning downstream or in parallel with Numb. These findings uncover a previously unknown function of Lgl in the inhibition of Notch and reveal different modes of action by which Lgl can influence cell fate in the neuroblast and SOP lineages.
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bazooka is required for localization of determinants and controlling proliferation in the Sensory Organ precursor cell lineage in drosophila
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Fabrice Roegiers, Lily Yeh Jan, Susan Youngershepherd, Yuh Nung JanAbstract:Asymmetric divisions with two different division orientations follow different polarity cues for the asymmetric segregation of determinants in the Sensory Organ precursor (SOP) lineage. The first asymmetric division depends on frizzled function and has the mitotic spindle of the pI cell in the epithelium oriented along the anterior–posterior axis, giving rise to pIIa and pIIb, which divide in different orientations. Only the pIIb division resembles neuroblast division in daughter-size asymmetry, spindle orientation along the apical–basal axis, basal Numb localization, and requirement for inscuteable function. Because the PDZ domain protein Bazooka is required for spindle orientation and basal localization of Numb in neuroblasts, we wondered whether Bazooka plays a similar role in the pIIb in the SOP lineage. Surprisingly, Bazooka controls asymmetric localization of the Numb-anchoring protein Pon, but not spindle orientation, in pI and all subsequent divisions. Bazooka also regulates cell proliferation in the SOP lineage; loss of bazooka function results in supernumerary cell divisions and apoptotic cell death.
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two types of asymmetric divisions in the drosophila Sensory Organ precursor cell lineage
Nature Cell Biology, 2001Co-Authors: Fabrice Roegiers, Lily Yeh Jan, Susan Youngershepherd, Yuh Nung JanAbstract:Asymmetric partitioning of cell-fate determinants during development requires coordinating the positioning of these determinants with orientation of the mitotic spindle. In the Drosophila peripheral nervous system, Sensory Organ progenitor cells (SOPs) undergo several rounds of division to produce five cells that give rise to a complete Sensory Organ. Here we have observed the asymmetric divisions that give rise to these cells in the developing pupae using green fluorescent protein fusion proteins. We find that spindle orientation and determinant localization are tightly coordinated at each division. Furthermore, we find that two types of asymmetric divisions exist within the Sensory Organ precursor cell lineage: the anterior-posterior pI cell-type division, where the spindle remains symmetric throughout mitosis, and the strikingly neuroblast-like apical-basal division of the pIIb cell, where the spindle exhibits a strong asymmetry at anaphase. In both these divisions, the spindle reorientates to position itself perpendicular to the region of the cortex containing the determinant. On the basis of these observations, we propose that two distinct mechanisms for controlling asymmetric cell divisions occur within the same lineage in the developing peripheral nervous system in Drosophila.
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a gain of function screen for genes that affect the development of the drosophila adult external Sensory Organ
Genetics, 2000Co-Authors: Salim Abdelilahseyfried, Lily Yeh Jan, Susan Youngershepherd, Yeeming Chan, Chaoyang Zeng, Nicholas J Justice, Linda Sharp, Sandra Barbel, Sarah Meadows, Yuh Nung JanAbstract:The Drosophila adult external Sensory Organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in Sensory Organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rorth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external Sensory Organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external Sensory Organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external Sensory Organs or subsets of Sensory Organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system.
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flamingo controls the planar polarity of Sensory bristles and asymmetric division of Sensory Organ precursors in drosophila
Current Biology, 1999Co-Authors: Tadao Usui, Tadashi Uemura, Lily Yeh Jan, Yuh Nung JanAbstract:Abstract The Sensory bristles of the fruit fly Drosophila are Organized in a polarized fashion such that bristles on the thorax point posteriorly. These bristles are derived from asymmetric division of Sensory Organ precursors (SOPs). The Numb protein, which is localized asymmetrically in a cortical crescent in each SOP, segregates into only one of the two daughter cells during cell division, thereby conferring distinct fates to the daughter cells [1,2]. In neuroblasts, establishment of apical–basal polarity by the protein Inscuteable is crucial for orienting asymmetric division, but this is not the case for division of SOPs [3]. Instead, the Frizzled (Fz) protein mediates a planar polarity signal that controls the anteroposteriorly oriented first division (pl) of SOPs [4]. Here, we report that Flamingo (Fmi), a seven-transmembrane cadherin [5], controls the planar polarity of Sensory bristles and the orientation of the SOP pl division. Both the loss of function and overexpression of fmi disrupted bristle polarity. During mitosis of the SOP, the axis of the pl division and the positioning of the Numb crescent were randomized in the absence of Fmi activity. Overexpression of Fmi and Fz caused similar effects. The dependence of proper Fmi localization on Fz activity suggests that Fmi functions downstream of Fz in controlling planar polarity. We also present evidence suggesting that Fz also functions in the Wingless pathway to pattern Sensory Organs.
Hugo J Bellen - One of the best experts on this subject based on the ideXlab platform.
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the arp2 3 complex and wasp are required for apical trafficking of delta into microvilli during cell fate specification of Sensory Organ precursors
Nature Cell Biology, 2009Co-Authors: Akhila Rajan, Anchi Tien, Claire Haueter, Karen L Schulze, Hugo J BellenAbstract:Cell fate decisions mediated by Notch signalling generally involve direct cell–cell contact between adjacent cells. A new Arp2/3-dependent actin structure directs the Notch ligand Delta to microvilli in signal-sending cells during Sensory Organ development in fly.
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sec15 a component of the exocyst promotes notch signaling during the asymmetric division of drosophila Sensory Organ precursors
Developmental Cell, 2005Co-Authors: Hugo J Bellen, Hamed Jafarnejad, Hillary K Andrews, Melih Acar, Vafa Bayat, Frederik Wirtzpeitz, Sunil Q Mehta, Juergen A KnoblichAbstract:Summary Asymmetric division of Sensory Organ precursors (SOPs) in Drosophila generates different cell types of the mature Sensory Organ. In a genetic screen designed to identify novel players in this process, we have isolated a mutation in Drosophila sec15 , which encodes a component of the exocyst, an evolutionarily conserved complex implicated in intracellular vesicle transport. sec15 − Sensory Organs contain extra neurons at the expense of support cells, a phenotype consistent with loss of Notch signaling. A vesicular compartment containing Notch, Sanpodo, and endocytosed Delta accumulates in basal areas of mutant SOPs. Based on the dynamic traffic of Sec15, its colocalization with the recycling endosomal marker Rab11, and the aberrant distribution of Rab11 in sec15 clones, we propose that a defect in Delta recycling causes cell fate transformation in sec15 − Sensory lineages. Our data indicate that Sec15 mediates a specific vesicle trafficking event to ensure proper neuronal fate specification in Drosophila .
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senseless acts as a binary switch during Sensory Organ precursor selection
Genes & Development, 2003Co-Authors: Hamed Jafarnejad, Riitta Nolo, Melih Acar, Haluk Lacin, Hongling Pan, Susan M Parkhurst, Hugo J BellenAbstract:During Sensory Organ precursor (SOP) specification, a single cell is selected from a proneural cluster of cells. Here, we present evidence that Senseless (Sens), a zinc-finger transcription factor, plays an important role in this process. We show that Sens is directly activated by proneural proteins in the presumptive SOPs and a few cells surrounding the SOP in most tissues. In the cells that express low levels of Sens, it acts in a DNA-binding-dependent manner to repress transcription of proneural genes. In the presumptive SOPs that express high levels of Sens, it acts as a transcriptional activator and synergizes with proneural proteins. We therefore propose that Sens acts as a binary switch that is fundamental to SOP selection.
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senseless a zn finger transcription factor is necessary and sufficient for Sensory Organ development in drosophila
Cell, 2000Co-Authors: Riitta Nolo, Lois A Abbott, Hugo J BellenAbstract:The senseless (sens) gene is required for proper development of most cell types of the embryonic and adult peripheral nervous system (PNS) of Drosophila. Sens is a nuclear protein with four Zn fingers that is expressed and required in the Sensory Organ precursors (SOP) for proper proneural gene expression. Ectopic expression of Sens in many ectodermal cells causes induction of PNS external Sensory Organ formation and is able to recreate an ectopic proneural field. Hence, sens is both necessary and sufficient for PNS development. Our data indicate that proneural genes activate sens expression. Sens is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs.
