The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
James B Skeath - One of the best experts on this subject based on the ideXlab platform.
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at the nexus between pattern formation and cell type specification the generation of individual Neuroblast fates in the drosophila embryonic central nervous system
BioEssays, 1999Co-Authors: James B SkeathAbstract:The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed Neuroblasts. Neuroblasts arise from the ectoderm in an invariant pattern, and each Neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of Neuroblasts. One group, the segment polarity genes, enables Neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that Neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual Neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc.
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the drosophila egf receptor controls the formation and specification of Neuroblasts along the dorsal ventral axis of the drosophila embryo
Development, 1998Co-Authors: James B SkeathAbstract:The segmented portion of the Drosophila embryonic central nervous system develops from a bilaterally symmetrical, segmentally reiterated array of 30 unique neural stem cells, called Neuroblasts. The first 15 Neuroblasts form about 30–60 minutes after gastrulation in two sequential waves of Neuroblast segregation and are arranged in three dorsoventral columns and four anteroposterior rows per hemisegment. Each Neuroblast acquires a unique identity, based on gene expression and the unique and nearly invariant cell lineage it produces. Recent experiments indicate that the segmentation genes specify Neuroblast identity along the AP axis. However, little is known as to the control of Neuroblast identity along the DV axis. Here, I show that the Drosophila EGF receptor (encoded by the DER gene) promotes the formation, patterning and individual fate specification of early forming Neuroblasts along the DV axis. Specifically, I use molecular markers that identify particular neuroectodermal domains, all Neuroblasts or individual Neuroblasts, to show that in DER mutant embryos (1) intermediate column Neuroblasts do not form, (2) medial column Neuroblasts often acquire identities inappropriate for their position, while (3) lateral Neuroblasts develop normally. Furthermore, I show that active DER signaling occurs in the regions from which the medial and intermediate Neuroblasts will later delaminate. In addition, I demonstrate that the concomitant loss of rhomboid and vein yield CNS phenotypes indistinguishable from DER mutant embryos, even though loss of either gene alone yields minor CNS phenotypes. These results demonstrate that DER plays a critical role during Neuroblast formation, patterning and specification along the DV axis within the developing Drosophila embryonic CNS.
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new Neuroblast markers and the origin of the acc pcc neurons in the drosophila central nervous system
Mechanisms of Development, 1995Co-Authors: Julie Broadus, James B Skeath, Eric P Spana, Torsten Bossing, Gerhard M TechnauAbstract:Drosophila is an ideal system for identifying genes that control central nervous system (CNS) development. Particularly useful tools include molecular markers for subsets of neural precursors (Neuroblasts) and the simple expression pattern of the even-skipped (eve) gene in a subset of neurons. Here we provide additional molecular markers for identified Neuroblasts, including several with near single cell specificity. In addition, we use these new markers to trace the development of several eve+ neurons. Our results shows that the eve+ aCC/pCC neurons develop from a different Neuroblast than previously thought, and have led us to assign new names for several Neuroblasts. These results are supported by DiI cell lineage analysis of Neuroblasts identified in vivo.
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Specification of Neuroblast identity in the Drosophila embryonic central nervous system by gooseberry-distal
Nature, 1995Co-Authors: James B Skeath, Yu Zhang, Robert A. Holmgren, Sean B. CarrollAbstract:THE Drosophila central nervous system develops from a segment-ally reiterated array of 30 unique neural precursors, called neuro-blasts. Each Neuroblast goes through a stereotyped cell lineage to produce an invariant clone of neural progeny. It is critical to identify the genes that specify Neuroblast identity as these genes control the time of formation, gene expression profile, and cell lineage characteristics of each Neuroblast. Here we show that the Pax-type gooseberry-distal gene specifies row 5 Neuroblast identity. Initially, four rows of Neuroblasts form per segment (1,3,5,7) and gooseberry-distal is expressed in row 5 Neuroblasts1a¤-3. By using 10 molecular markers, and by following the number and orientation of Neuroblast divisions, we show that lack of gooseberry-distal transforms row 5 Neuroblasts into row 3 Neuroblasts, whereas ubiquitous gooseberry-distal generates the reciprocal transformation. Thus, gooseberry-distal is necessary and sufficient to specify row 5 Neuroblast identity autonomously. The 10 genes coordinately regulated by gooseberry-distal are prime candidates for controlling specific aspects of Neuroblast identity.
Kristin White - One of the best experts on this subject based on the ideXlab platform.
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a cut cohesin axis alters the chromatin landscape to facilitate Neuroblast death
Development, 2019Co-Authors: Richa Arya, Seda Gyonjyan, Katherine Harding, Tatevik Sarkissian, Ying Li, Lei Zhou, Kristin WhiteAbstract:ABSTRACT Precise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (Neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer. The activity of this enhancer is controlled by abdominal A and Notch, but additional inputs are needed for proper specificity. Here, we show that the Cut DNA binding protein is required for Neuroblast death, regulating reaper and grim downstream of the shared enhancer and of abdominal A expression. The loss of cut accelerates the temporal progression of Neuroblasts from a state of low overall levels of H3K27me3 to a higher H3K27me3 state. This is reflected in an increase in H3K27me3 modifications in the cell death gene locus in the CNS on Cut knockdown. We also show that cut regulates the expression of the cohesin subunit Stromalin. Stromalin and the cohesin regulatory subunit Nipped-B are required for Neuroblast death, and knockdown of Stromalin increases H3K27me3 levels in Neuroblasts. Thus, Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.
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a cut cohesin axis alters the chromatin landscape to facilitate Neuroblast death
bioRxiv, 2018Co-Authors: Richa Arya, Seda Gyonjyan, Katherine Harding, Tatevik Sarkissian, Ying Li, Lei Zhou, Kristin WhiteAbstract:Precise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (Neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer, enh1. The activity of enh1 is controlled by abdominalA and Notch, but additional inputs are needed for proper specificity. Here we show that the Cut DNA binding protein is required for Neuroblast death, acting downstream of enh1. In the nervous system, Cut promotes an open chromatin conformation in the cell death gene locus, allowing cell death gene expression in response to abdominalA. We demonstrate a temporal increase in global H3K27me3 levels in Neuroblasts, which is enhanced by cut knockdown. Furthermore, cut regulates the expression of the cohesin subunit Stromalin in the nervous system. The cohesin components Stromalin and NippedB are required for Neuroblast death, and knockdown of Stromalin increases repressive histone modifications in Neuroblasts. Thus Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.
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coordinated expression of cell death genes regulates Neuroblast apoptosis
Development, 2011Co-Authors: Megumu Yamadamabuchi, Richa Arya, Susan E St Pierre, Wei Tang, Marie I Tosa, Carrie Baker Brachmann, Kristin WhiteAbstract:Properly regulated apoptosis in the developing central nervous system is crucial for normal morphogenesis and homeostasis. In Drosophila, a subset of neural stem cells, or Neuroblasts, undergo apoptosis during embryogenesis. Of the 30 Neuroblasts initially present in each abdominal hemisegment of the embryonic ventral nerve cord, only three survive into larval life, and these undergo apoptosis in the larvae. Here, we use loss-of-function analysis to demonstrate that Neuroblast apoptosis during embryogenesis requires the coordinated expression of the cell death genes grim and reaper, and possibly sickle. These genes are clustered in a 140 kb region of the third chromosome and show overlapping patterns of expression. We show that expression of grim, reaper and sickle in embryonic Neuroblasts is controlled by a common regulatory region located between reaper and grim. In the absence of grim and reaper, many Neuroblasts survive the embryonic period of cell death and the ventral nerve cord becomes massively hypertrophic. Deletion of grim alone blocks the death of Neuroblasts in the larvae. The overlapping activity of these multiple cell death genes suggests that the coordinated regulation of their expression provides flexibility in this crucial developmental process.
Richa Arya - One of the best experts on this subject based on the ideXlab platform.
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a cut cohesin axis alters the chromatin landscape to facilitate Neuroblast death
Development, 2019Co-Authors: Richa Arya, Seda Gyonjyan, Katherine Harding, Tatevik Sarkissian, Ying Li, Lei Zhou, Kristin WhiteAbstract:ABSTRACT Precise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (Neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer. The activity of this enhancer is controlled by abdominal A and Notch, but additional inputs are needed for proper specificity. Here, we show that the Cut DNA binding protein is required for Neuroblast death, regulating reaper and grim downstream of the shared enhancer and of abdominal A expression. The loss of cut accelerates the temporal progression of Neuroblasts from a state of low overall levels of H3K27me3 to a higher H3K27me3 state. This is reflected in an increase in H3K27me3 modifications in the cell death gene locus in the CNS on Cut knockdown. We also show that cut regulates the expression of the cohesin subunit Stromalin. Stromalin and the cohesin regulatory subunit Nipped-B are required for Neuroblast death, and knockdown of Stromalin increases H3K27me3 levels in Neuroblasts. Thus, Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.
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a cut cohesin axis alters the chromatin landscape to facilitate Neuroblast death
bioRxiv, 2018Co-Authors: Richa Arya, Seda Gyonjyan, Katherine Harding, Tatevik Sarkissian, Ying Li, Lei Zhou, Kristin WhiteAbstract:Precise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (Neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer, enh1. The activity of enh1 is controlled by abdominalA and Notch, but additional inputs are needed for proper specificity. Here we show that the Cut DNA binding protein is required for Neuroblast death, acting downstream of enh1. In the nervous system, Cut promotes an open chromatin conformation in the cell death gene locus, allowing cell death gene expression in response to abdominalA. We demonstrate a temporal increase in global H3K27me3 levels in Neuroblasts, which is enhanced by cut knockdown. Furthermore, cut regulates the expression of the cohesin subunit Stromalin in the nervous system. The cohesin components Stromalin and NippedB are required for Neuroblast death, and knockdown of Stromalin increases repressive histone modifications in Neuroblasts. Thus Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.
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coordinated expression of cell death genes regulates Neuroblast apoptosis
Development, 2011Co-Authors: Megumu Yamadamabuchi, Richa Arya, Susan E St Pierre, Wei Tang, Marie I Tosa, Carrie Baker Brachmann, Kristin WhiteAbstract:Properly regulated apoptosis in the developing central nervous system is crucial for normal morphogenesis and homeostasis. In Drosophila, a subset of neural stem cells, or Neuroblasts, undergo apoptosis during embryogenesis. Of the 30 Neuroblasts initially present in each abdominal hemisegment of the embryonic ventral nerve cord, only three survive into larval life, and these undergo apoptosis in the larvae. Here, we use loss-of-function analysis to demonstrate that Neuroblast apoptosis during embryogenesis requires the coordinated expression of the cell death genes grim and reaper, and possibly sickle. These genes are clustered in a 140 kb region of the third chromosome and show overlapping patterns of expression. We show that expression of grim, reaper and sickle in embryonic Neuroblasts is controlled by a common regulatory region located between reaper and grim. In the absence of grim and reaper, many Neuroblasts survive the embryonic period of cell death and the ventral nerve cord becomes massively hypertrophic. Deletion of grim alone blocks the death of Neuroblasts in the larvae. The overlapping activity of these multiple cell death genes suggests that the coordinated regulation of their expression provides flexibility in this crucial developmental process.
Gerhard M Technau - One of the best experts on this subject based on the ideXlab platform.
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Abdominal-B and caudal inhibit the formation of specific Neuroblasts in the Drosophila tail region
Development, 2013Co-Authors: Oliver Birkholz, Ana Rogulja-ortmann, Christian Berger, Gerhard M TechnauAbstract:The central nervous system of Drosophila melanogaster consists of fused segmental units (neuromeres), each generated by a characteristic number of neural stem cells (Neuroblasts). In the embryo, thoracic and anterior abdominal neuromeres are almost equally sized and formed by repetitive sets of Neuroblasts, whereas the terminal abdominal neuromeres are generated by significantly smaller populations of progenitor cells. Here we investigated the role of the Hox gene Abdominal-B in shaping the terminal neuromeres. We show that the regulatory isoform of Abdominal-B (Abd-B.r) not only confers abdominal fate to specific Neuroblasts (e.g. NB6-4) and regulates programmed cell death of several progeny cells within certain Neuroblast lineages (e.g. NB3-3) in parasegment 14, but also inhibits the formation of a specific set of Neuroblasts in parasegment 15 (including NB7-3). We further show that Abd-B.r requires cooperation of the ParaHox gene caudal to unfold its full competence concerning Neuroblast inhibition and specification. Thus, our findings demonstrate that combined action of Abdominal-B and caudal contributes to the size and composition of the terminal neuromeres by regulating both the number and lineages of specific Neuroblasts.
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Neuroblast pattern and identity in the Drosophila tail region and role of doublesex in the survival of sex-specific precursors
Development, 2013Co-Authors: Oliver Birkholz, Rolf Urbach, Christof Rickert, Christian Berger, Gerhard M TechnauAbstract:The central nervous system is composed of segmental units (neuromeres), the size and complexity of which evolved in correspondence to their functional requirements. In Drosophila , neuromeres develop from populations of neural stem cells (Neuroblasts) that delaminate from the early embryonic neuroectoderm in a stereotyped spatial and temporal pattern. Pattern units closely resemble the ground state and are rather invariant in thoracic (T1-T3) and anterior abdominal (A1-A7) segments of the embryonic ventral nerve cord. Here, we provide a comprehensive Neuroblast map of the terminal abdominal neuromeres A8-A10, which exhibit a progressively derived character. Compared with thoracic and anterior abdominal segments, Neuroblast numbers are reduced by 28% in A9 and 66% in A10 and are almost entirely absent in the posterior compartments of these segments. However, all Neuroblasts formed exhibit serial homology to their counterparts in more anterior segments and are individually identifiable based on their combinatorial code of marker gene expression, position, delamination time point and the presence of characteristic progeny cells. Furthermore, we traced the embryonic origin and characterised the postembryonic lineages of a set of terminal Neuroblasts, which have been previously reported to exhibit sex-specific proliferation behaviour during postembryonic development. We show that the respective sex-specific product of the gene doublesex promotes programmed cell death of these Neuroblasts in females, and is needed for their survival, but not proliferation, in males. These data establish the terminal neuromeres as a model for further investigations into the mechanisms controlling segment- and sex-specific patterning in the central nervous system.
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Segment polarity and DV patterning gene expression reveals segmental organization of the Drosophila brain.
Development, 2003Co-Authors: Rolf Urbach, Gerhard M TechnauAbstract:The insect brain is traditionally subdivided into the trito-, deuto- and protocerebrum. However, both the neuromeric status and the course of the borders between these regions are unclear. The Drosophila embryonic brain develops from the procephalic neurogenic region of the ectoderm, which gives rise to a bilaterally symmetrical array of about 100 neuronal precursor cells, called Neuroblasts. Based on a detailed description of the spatiotemporal development of the entire population of embryonic brain Neuroblasts, we carried out a comprehensive analysis of the expression of segment polarity genes ( engrailed, wingless, hedgehog, gooseberry distal, mirror ) and DV patterning genes ( muscle segment homeobox, intermediate Neuroblast defective, ventral nervous system defective ) in the procephalic neuroectoderm and the Neuroblast layer (until stage 11, when all Neuroblasts are formed). The data provide new insight into the segmental organization of the procephalic neuroectodem and evolving brain. The expression patterns allow the drawing of clear demarcations between trito-, deuto- and protocerebrum at the level of identified Neuroblasts. Furthermore, we provide evidence indicating that the protocerebrum (most anterior part of the brain) is composed of two neuromeres that belong to the ocular and labral segment, respectively. These protocerebral neuromeres are much more derived compared with the trito- and deutocerebrum. The labral neuromere is confined to the posterior segmental compartment. Finally, similarities in the expression of DV patterning genes between the Drosophila and vertebrate brains are discussed.
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Molecular markers for identified Neuroblasts in the developing brain of Drosophila
Development, 2003Co-Authors: Rolf Urbach, Gerhard M TechnauAbstract:The Drosophila brain develops from the procephalic neurogenic region of the ectoderm. About 100 neural precursor cells (Neuroblasts) delaminate from this region on either side in a reproducible spatiotemporal pattern. We provide Neuroblast maps from different stages of the early embryo (stages 9, 10 and 11, when the entire population of Neuroblasts has formed), in which about 40 molecular markers representing the expression patterns of 34 different genes are linked to individual Neuroblasts. In particular, we present a detailed description of the spatiotemporal patterns of expression in the procephalic neuroectoderm and in the Neuroblast layer of the gap genes empty spiracles, hunchback, huckebein, sloppy paired 1 and tailless ; the homeotic gene labial ; the early eye genes dachshund, eyeless and twin of eyeless ; and several other marker genes (including castor, pdm1, fasciclin 2, klumpfuss, ladybird, runt and unplugged ). We show that based on the combination of genes expressed, each brain Neuroblast acquires a unique identity, and that it is possible to follow the fate of individual Neuroblasts through early neurogenesis. Furthermore, despite the highly derived patterns of expression in the procephalic segments, the co-expression of specific molecular markers discloses the existence of serially homologous Neuroblasts in neuromeres of the ventral nerve cord and the brain. Taking into consideration that all brain Neuroblasts are now assigned to particular neuromeres and individually identified by their unique gene expression, and that the genes found to be expressed are likely candidates for controlling the development of the respective Neuroblasts, our data provide a basic framework for studying the mechanisms leading to pattern and cell diversity in the Drosophila brain, and for addressing those mechanisms that make the brain different from the truncal CNS.
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the pattern of Neuroblast formation mitotic domains and proneural gene expression during early brain development in drosophila
Development, 2003Co-Authors: Rolf Urbach, Ralf Schnabel, Gerhard M TechnauAbstract:In the Drosophila embryo, studies on CNS development have so far mainly focused on the relatively simply structured ventral nerve cord. In the trunk, proneural genes become expressed in small cell clusters at specific positions of the ventral neuroectoderm. A lateral inhibition process mediated by the neurogenic genes ensures that only one cell within each proneural cluster delaminates as a neural stem cell (Neuroblast). Thus, a fixed number of Neuroblasts is formed, according to a stereotypical spatiotemporal and segmentally repeated pattern, each subsequently generating a specific cell lineage. Owing to higher complexity and hidden segmental organisation, the mechanisms underlying the development of the brain are much less understood. In order to pave the way towards gaining deeper insight into these mechanisms, we have undertaken a comprehensive survey of early brain development until embryonic stage 11, when all brain Neuroblasts have formed. We describe the complete spatiotemporal pattern of formation of about 100 brain Neuroblasts on either side building the trito-, deuto- and protocerebrum. Using 4D-microscopy, we have uncovered various modes of Neuroblast formation that are related to specific mitotic domains of the procephalic neuroectoderm. Furthermore, a detailed description is provided of the dynamic expression patterns of proneural genes ( achaete, scute, lethal of scute, atonal ) in the procephalic neuroectoderm and the individual Neuroblasts. Finally, we present direct evidence that, in contrast to the trunk, adjacent cells within specific domains of the procephalic neuroectoderm develop as Neuroblasts, indicating that mechanisms controlling Neuroblast formation differ between head and trunk.
Clemens Cabernard - One of the best experts on this subject based on the ideXlab platform.
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Drosophila melanogaster Neuroblasts: A Model for Asymmetric Stem Cell Divisions.
Results and problems in cell differentiation, 2017Co-Authors: Emmanuel Gallaud, Tri Thanh Pham, Clemens CabernardAbstract:Asymmetric cell division (ACD) is a fundamental mechanism to generate cell diversity, giving rise to daughter cells with different developmental potentials. ACD is manifested in the asymmetric segregation of proteins or mRNAs, when the two daughter cells differ in size or are endowed with different potentials to differentiate into a particular cell type (Horvitz and Herskowitz, Cell 68:237–255, 1992). Drosophila Neuroblasts, the neural stem cells of the developing fly brain, are an ideal system to study ACD since this system encompasses all of these characteristics. Neuroblasts are intrinsically polarized cells, utilizing polarity cues to orient the mitotic spindle, segregate cell fate determinants asymmetrically, and regulate spindle geometry and physical asymmetry. The Neuroblast system has contributed significantly to the elucidation of the basic molecular mechanisms underlying ACD. Recent findings also highlight its usefulness to study basic aspects of stem cell biology and tumor formation. In this review, we will focus on what has been learned about the basic mechanisms underlying ACD in fly Neuroblasts.
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apical basal spindle orientation is required for Neuroblast homeostasis and neuronal differentiation in drosophila
Developmental Cell, 2009Co-Authors: Clemens CabernardAbstract:Precise regulation of stem cell self-renewal/differentiation is essential for embryogenesis and tumor suppression. Drosophila neural progenitors (Neuroblasts) align their spindle along an apical/basal polarity axis to generate a self-renewed apical Neuroblast and a differentiating basal cell. Here, we genetically disrupt spindle orientation without altering cell polarity to test the role of spindle orientation in self-renewal/differentiation. We perform correlative live imaging of polarity markers and spindle orientation over multiple divisions within intact brains, followed by molecular marker analysis of cell fate. We find that spindle alignment orthogonal to apical/basal polarity always segregates apical determinants into both siblings, which invariably assume a Neuroblast identity. Basal determinants can all be localized into one sibling without inducing neuronal differentiation, but overexpression of the basal determinant Prospero can deplete Neuroblasts. We conclude that the ratio of apical/basal determinants specifies Neuroblast/GMC identity, and that apical/basal spindle orientation is required for Neuroblast homeostasis and neuronal differentiation.
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drosophila aurora a kinase inhibits Neuroblast self renewal by regulating apkc numb cortical polarity and spindle orientation
Genes & Development, 2006Co-Authors: Ryan O Andersen, Clemens Cabernard, Laurina Manning, Khoa D Tran, Marcus J Lanskey, Arash BashirullahAbstract:Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis. Drosophila larval Neuroblasts divide asymmetrically to self-renew, and are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain Neuroblast numbers that map to the aurora-A gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in aurora-A mutants show single Neuroblasts generate multiple Neuroblasts (ectopic self-renewal). This phenotype is due to two independent Neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis. numb mutant clones have ectopic Neuroblasts, and Numb overexpression partially suppresses aurora-A Neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased Neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of Neuroblast self-renewal and that spindle orientation regulates Neuroblast self-renewal.