Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila
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{"title"=>"Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila", "type"=>"journal", "authors"=>[{"first_name"=>"Henrike", "last_name"=>"Becker", "scopus_author_id"=>"57188702177"}, {"first_name"=>"Simone", "last_name"=>"Renner", "scopus_author_id"=>"23091904700"}, {"first_name"=>"Gerhard M.", "last_name"=>"Technau", "scopus_author_id"=>"7003708965"}, {"first_name"=>"Christian", "last_name"=>"Berger", "scopus_author_id"=>"57193786054"}], "year"=>2016, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537404", "sgr"=>"84962424498", "doi"=>"10.1371/journal.pgen.1005961", "pmid"=>"27015425", "scopus"=>"2-s2.0-84962424498", "pui"=>"609631150"}, "id"=>"72927f76-8536-36db-abc0-b1a36226e676", "abstract"=>"During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Antennapedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental patterning in the developing CNS.", "link"=>"http://www.mendeley.com/research/cellautonomous-noncellautonomous-function-hox-genes-specify-segmental-neuroblast-identity-gnathal-re", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>1, "Neuroscience"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4869682"], "description"=>"<p>(A) Single mutation of <i>Abl</i><sup><i>1</i></sup> shows no transformation in NB6-4max. (B) Double mutants for <i>Ama</i><sup><i>M109</i></sup> and <i>Abl</i><sup><i>1</i></sup> with an Abl rescue construct (<i>Abl</i><sup>+</sup>) show only a minor transformation rate of 10%. (C) The mutant allele <i>Abl</i><sup><i>4</i></sup> that has no kinase activity shows a transformation of NB6-4max in 41% of all hemisegments. (D) Mutation of the Abl interacting protein <i>Dab</i><sup><i>1</i></sup> shows a transformation of NB6-4max in 40% (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.g004\" target=\"_blank\">Fig 4A</a>) of all hemisegments. (E) Double mutants for <i>Abl</i><sup><i>4</i></sup> and <i>Dfd</i><sup><i>16</i></sup> that interrupt both pathways show a transformation of NB6-4max in 95% of all hemisegments. (F) In the left panel: Abl (magenta) is localized in the cytoplasm with cortical enhancement in wild type NB6-4max (Eg, green; magenta arrow heads) and other NBs (white arrow heads). The labial NB6-4 has divided already (yellow arrow heads). In <i>lab</i><sup><i>1</i></sup> and <i>Dfd</i><sup><i>12</i></sup> (100% transformation of NB6-4max) double mutants (right panel) the cortical localization of Abl is disrupted. Middle panel show the Abl channel in monochrome. Lower panel show pixel intensity tracks of Abl staining across a line drawn through the cell (colors indicate corresponding line in the middle panel). In wild type (left part) NB6-4max and one other NBs as an example shows stronger pixel intensities towards the cell cortex (blue bars). This is lost in the transformed glial (GB) and neuronal precursor (NB) of NB6-4max or other NBs in the <i>lab</i><sup><i>1</i></sup> and <i>Dfd</i><sup><i>12</i></sup> double mutant situation (right part). (G) Transformed NB6-4 in maxillary segments of <i>Abl</i><sup><i>4</i></sup> mutant shows normal expression of Dfd (red) in early st11 (left panel) and late st11 (right panel) of lineage development. Lower panel show Dfd channel in monochrome. (H) Re-expression of <i>Abl</i> using the <i>sca</i>Gal4 line rescues the transformation phenotype of NB6-4max in 20% of all hemisegments in <i>lab</i><sup><i>1</i></sup><i>/Dfd</i><sup><i>12</i></sup> double mutants (left panel) or 40% in <i>Dfd</i><sup><i>16</i></sup><i>/Antp</i><sup><i>7</i></sup> double mutants (right panel). Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130240, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Amalgam_Nrt_act_via_Disabled_regulating_Abelson_tyrosine_kinase_function_to_specify_NB6_4max_identity_/3130240", "title"=>"Amalgam/Nrt act via Disabled regulating Abelson tyrosine kinase function to specify NB6-4max identity.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869652"], "description"=>"<p>(A) Mutant mini-screen for potential Hox target genes influencing NB6-4max segmental specification. Transformation rates of NB6-4max are given in percentage of analyzed maxillary hemisegments (number of hemisegments see text). (B) Double mutation of <i>Abl</i><sup><i>1</i></sup> and <i>Ama</i><sup><i>R1</i></sup> leads to a transformation of NB6-4max into a neuroglioblast in 29% of all hemisegments. (C) Mutation of <i>Nrt</i><sup><i>1</i></sup> leads to a transformation of NB6-4max into a neuroglioblast in 15% of all hemisegments. (D) Distribution of <i>Ama</i> mRNA (in green) in the neuroectoderm/nervous system of gnathal segments at early stage 10 (left panel), early stage 11 (middle panel) and late stage 11 (right panel) by <i>in situ</i> hybridization; lower panel displays corresponding channel in monochrome. The segmental marker Engrailed (En) is shown in magenta. Yellow box indicates parasegment 2 that is determined by Scr and shows reduced expression of <i>Ama</i> mRNA. (E-H) <i>Ama</i> mRNA expression (green; lower panel monochrome) in mutant backgrounds; compare to wild type expression shown in the middle panel of (D) at early stage 11. (E) <i>Scr</i><sup><i>17</i></sup> mutation shows up-regulation of <i>Ama</i> mRNA expression in parasegment 2 indicated by the yellow box. (F) <i>Dfd</i><sup><i>16</i></sup> mutation shows down-regulation of <i>Ama</i> mRNA expression in posterior mandibular and maxillary regions (yellow box). (G) Double mutation for <i>lab</i><sup><i>1</i></sup> and <i>Dfd</i><sup><i>12</i></sup> shows down-regulation of <i>Ama</i> mRNA expression in mandibular and maxillary regions (yellow box). (H) Double mutation for <i>Dfd</i><sup><i>16</i></sup> and <i>Antp</i><sup><i>7</i></sup> shows down-regulation of <i>Ama</i> mRNA expression in the region of mandibular to thoracic segments (yellow box). (I) Distribution of Ama protein (in green) in the neuroectoderm/nervous system of gnathal segments at stage 10 (left panel), early stage 11 (middle panel) and late stage 11 (right panel) by antibody staining. Lower panel shows corresponding Ama channel in monochrome. In magenta is the segmental marker En. Red box indicates the region of NB6-4max. Orange box indicates the distribution of Ama in mandibular and more anterior regions. (J, K) Compare the Ama expression patterns to the wild type expression shown in the middle panel of (I) at stage 10. (J) <i>Dfd</i><sup><i>16</i></sup> mutation shows no significant change of Ama protein distribution in the region of NB6-4max (red box) presumably due to secreted Ama invading from anterior (orange box) and posterior source. (K) Double mutation for <i>lab</i><sup><i>1</i></sup> and <i>Dfd</i><sup><i>12</i></sup> shows reduced Ama distribution in the region of NB6-4max and significant reduction of Ama in more anterior regions (orange box). (L) Transheterozygous mutation for the deficiency Df(3R)BSC467 covering <i>Dfd</i> and <i>Ama</i> and <i>Abl</i><sup><i>1</i></sup>, <i>Ama</i><sup><i>R1</i></sup> shows an increase in the transformation rate to 50% in NB6-4max suggesting a synergistic effect of the Dfd- and the Ama-pathway. (M) Heatshock-induced expression of <i>Ama</i> in the <i>lab</i><sup><i>1</i></sup>/<i>Dfd</i><sup><i>12</i></sup> double mutant rescues the transformation phenotype of NB6-4max in 40% of all hemisegments leading to an overall transformation of 60% (<i>lab</i><sup><i>1</i></sup>/<i>Dfd</i><sup><i>12</i></sup> show 100% transformation). Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130210, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_mini_screen_for_novel_regulators_of_NB6_4max_specification_identifies_the_secreted_protein_Amalgam_as_potential_Hox_target_/3130210", "title"=>"A mini-screen for novel regulators of NB6-4max specification identifies the secreted protein Amalgam as potential Hox target.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869556"], "description"=>"<p>(A) Identification of Eagle (Eg) expressing neuroblasts (NBs) in filet preparations of wild type gnathal CNS segments at embryonic stage 11. NBs were stained with Deadpan (Dpn) antibody (magenta); NBs 3–3, 6–4 and 7–3 were identified by co-staining with Eg antibody (green). Middle panel shows Eg channel in monochrome, right panel shows Dpn channel in monochrome. (B) NB3-3 can be identified by co-staining of Eg and Runt antibody (red), NB7-3 can be identified by co-staining of Eg and the segmental marker En (blue) and its typical dorso-medial position. (C) Co-staining of Eg (green), En (white), Dpn (blue) and Gooseberry (Gsb, red) antibody identifies NB6-4 and the presence of Gsb-positive/Eg-negative NB6-2, NB7-1 and NB6-1. (D) Additional cells (cyan circles) express Eg from stage 13 onwards. Progeny of MNB can be identified in the midline of mad and max segments and progeny of NB5-3 can be identified in all three segments. For identification of these cells see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.s001\" target=\"_blank\">S1 Fig</a> (E) Schematics of the core Eg expression pattern at stage 16. For simplicity extra Eg-positive cells are not highlighted. For complete pattern see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.s001\" target=\"_blank\">S1</a> and <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.s002\" target=\"_blank\">S2</a> Figs. (F) Co-staining of Eg (green) with Repo (magenta) antibody reveals a pure glial NB6-4 lineage in maxillary segment and a mixed neuronal/glial lineage in the labial segment. (G) At stage 12 the maxillary NB6-4 lineage consists of four glial cells (magenta arrow heads), two medial and two lateral cell-body glial cells. The labial NB6-4 generates a dorso-lateral cluster of 4–5 neurons (green arrow heads) and three cell-body glial cells (magenta arrow heads) of which one is located ventro-laterally and two are in a ventro-medial position. The left panels shows <i>eg</i>Gal4 expressing UAS-<i>CD4</i>::<i>gfp</i> to show the clonal relation and to identify the four glial cells in the maxillary segment. In this and all following figures if not stated differently: anterior is up, dashed white line represents the midline, dashed yellow lines indicate segmental boundaries, mad, mandibular segment, max, maxillary segment and lab, labial segment, numbers indicate NBs or NB-lineages (e.g. 7–3 indicates NB7-3), magenta arrow heads indicate NB6-4 glioblast or its glial progeny cells, green arrow heads indicate NB6-4 neuronal daughter precursor or neuronal progeny cells, WT, wild type, st, stage, l, late, e, early, m, middle. Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130147, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Description_of_the_Eagle_positive_Neuroblast_lineages_in_embryonic_gnathal_segments_/3130147", "title"=>"Description of the Eagle-positive Neuroblast-lineages in embryonic gnathal segments.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869625"], "description"=>"<p>For all images (A-J): Magenta arrow heads or spheres depict NB6-4-derived glial cells, green arrow heads or spheres depict NB6-4-derived neuronal cells. Segments are indicated. Right side shows an illustration of the composition of the NB6-4 lineage in the respective segments. Percentage gives transformation rate of NB6-4. (A) Wild type lineages of NB6-4 in maxillary and labial segments. NB6-4 generates 4 glial cells per maxillary hemisegment and 3 glial cells and a neuronal cluster per labial hemisegment. (B) In <i>Antennapedia</i> (<i>Antp</i><sup><i>25</i></sup>) mutants NB6-4 cell fate is not altered in maxillary or labial segments. (C) Ectopic expression of <i>Antp</i> using the <i>scabrous</i>-Gal4 (<i>sca</i>Gal4) line does not alter NB6-4 cell fates in maxillary or labial segments. (D) Mutation in <i>Deformed</i> (<i>Dfd</i><sup><i>16</i></sup>) leads to a transformation of NB6-4max glioblast into a neuroglioblast in 43% of all hemisegments. (E) Mutation in <i>Sex combs reduced</i> (<i>Scr</i><sup><i>17</i></sup>) leads to a transformation of NB6-4max glioblast into a neuroglioblast in 10% of all hemisegments. (F) Double mutation of <i>Dfd</i><sup><i>16</i></sup> and <i>Scr</i><sup><i>4</i></sup> leads to a reduction of the transformation rate (17%) compared to <i>Dfd</i> single mutants (Fig 3D, 43%). Dfd and Scr do not act synergistically. (G) Ectopic expression of <i>Scr</i> using the <i>scabrous</i>-Gal4 (<i>sca</i>Gal4) line does not alter NB6-4 cell fates in thoracic or labial (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.s004\" target=\"_blank\">S4A Fig</a>) segments. (H) Ectopic expression of <i>Dfd</i> using the <i>scabrous</i>-Gal4 (<i>sca</i>Gal4) line transforms thoracic and labial (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.s004\" target=\"_blank\">S4B Fig</a>) NB6-4 into a maxillary fate producing only glial cells in 74% of all thoracic hemisegments. (I) Double mutation of <i>lab</i><sup><i>1</i></sup> and <i>Dfd</i><sup><i>12</i></sup> leads to a complete transformation of NB6-4max glioblast fate into a labial/thoracic neuroglioblast fate in 100% of all hemisegments. (J) Double mutation of <i>Dfd</i><sup><i>16</i></sup> and <i>Antp</i><sup><i>7</i></sup> leads to a nearly complete transformation of NB6-4max glioblast fate into a labial/thoracic neuroglioblast fate in 87% of all hemisegments. (K) Summary diagram of transformation rates in NB6-4maxillar (grey bars) or NB6-4labial/thoracic (cyan bars) in the respective mutant or ectopic expression situation. Transformation rates are given in percentage of analyzed hemisegments (number of hemisegments see text). Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130189, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Segment_specificity_of_NB6_4max_is_primarily_determined_by_i_Deformed_i_but_influenced_in_a_parallel_mechanism_by_i_labial_i_and_i_Antennapedia_i_/3130189", "title"=>"Segment specificity of NB6-4max is primarily determined by <i>Deformed</i>, but influenced in a parallel mechanism by <i>labial</i> and <i>Antennapedia</i>.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869745"], "description"=>"<p>(A-C) In wild type neuroblasts stained with Dpn (blue) at stage 11 (A) a stable expression of Salvador (Sav, red) can be observed mirroring the active Hpo kinase. Mutation in <i>Abl</i><sup><i>4</i></sup> (B) or double mutation in <i>lab</i><sup><i>1</i></sup> and <i>Dfd</i><sup><i>12</i></sup> (C) show reduced Sav protein distribution, which argues for a less stable protein and an inactive Hpo kinase. Lower panel shows Sav channel in monochrome. (D) Yorkie (magenta) is localized to the cytoplasm of NB6-4max prior to its first division at stage 10. Cytoplasmically localized Yki is the inactive form of Yki. (E) Ectopic expression of a constitutive active form of <i>Yki</i><sup><i>CA</i></sup> using the <i>scabrous</i>-Gal4 (<i>sca</i>Gal4) line transforms NB6-4max in 29% of all maxillary hemisegments. (F) Triple mutation for <i>yki</i><sup><i>B5</i></sup> and <i>Abl</i><sup><i>4</i></sup>,<i>Dfd</i><sup><i>16</i></sup>, shows a decrease in the transformation rate from 100% in the double mutants for <i>Abl</i><sup><i>4</i></sup>,<i>Dfd</i><sup><i>16</i></sup> to 69% in the triple mutants. Thus, the loss of <i>yki</i> rescues the double mutant phenotype in 31% of all hemisegments. (G) Schematic model of the cell-autonomous and non-cell-autonomous regulation of maxillary identity specification of NB6-4. Expression pattern of Antp-C genes are shown color-coded in the CNS. In the posterior part of the maxillary segment Dfd and Scr are co-expressed. Lab, Dfd and Antp positively regulate the expression of Ama (brown areas and arrows), whereas Scr represses Ama expression. Ama binds to Nrt and via Dab activates Abl that leads to the repression of CycE expression presumably through the Hippo/Salvador/Warts pathway. Whether Abl influences the Hpo kinase or Yki itself needs to be further clarified. Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130288, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Abl_potentially_regulates_i_CycE_i_expression_via_the_Hippo_pathway_/3130288", "title"=>"Abl potentially regulates <i>CycE</i> expression via the Hippo pathway.", "pos_in_sequence"=>8, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869718"], "description"=>"<p>(A, B) In <i>Abl</i><sup><i>4</i></sup> (A) as well as in <i>Dfd</i><sup><i>16</i></sup> (B) mutant NB6-4max <i>CycE</i> is de-repressed and becomes distributed to the neuronal part of the transformed lineage. Whereas after the first division the glial daughter precursor (magenta circles and arrow heads, left panels) shows no <i>CycE</i> mRNA (red) the neuronal daughter precursor (green circles and arrow heads, right panels) shows clear <i>CycE</i> mRNA staining. (C) Wild type expression of <i>CycE</i> mRNA in the maxillary (magenta arrow heads) and labial NB6-4 (green arrow heads). In the maxillary segment only very weak expression of <i>CycE</i> mRNA can be found in NB6-4, whereas the labial NB6-4 shows a strong <i>CycE</i> mRNA expression. (D) Ectopic expression of <i>CycE</i> using the <i>scabrous</i>-Gal4 (<i>sca</i>Gal4) line transforms maxillary NB6-4 glioblast fate into labial/thoracic neuroglioblast fate in 12% of all hemisegments. (E) Mutation of <i>CycE</i><sup><i>AR95</i></sup> shows loss of the labial NB6-4 fate with only glia cells produced in 64% of all labial hemisegments. (F) Ectopic expression of <i>Dfd</i> using the <i>scabrous</i>-Gal4 (<i>sca</i>Gal4) line transforms labial/thoracic NB6-4 into a maxillary fate, generating four glial cells and no neuronal cells in 74% of all thoracic hemisegments. At this stage (st12e) no <i>CycE</i> mRNA (red) is observable in NB6-4 derived glial cells. (G) Loss of <i>CycE</i> in the <i>Dfd</i><sup><i>11</i></sup> single mutant leads to a rescue of the transformation phenotype of NB6-4max in 77% of all hemisegments. <i>CycE</i><sup><i>AR95</i></sup> mutation also leads to the loss of neuronal cells in the thoracic segments. (H) Loss of <i>CycE</i> in the <i>Abl</i><sup><i>4</i></sup>,<i>Dfd</i><sup><i>16</i></sup> double mutants leads to a rescue of the transformation phenotype of NB6-4max in 85% of all hemisegments. Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130261, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dfd_and_Abl_specify_maxillary_identity_of_NB6_4_lineages_by_repressing_i_CycE_i_/3130261", "title"=>"Dfd and Abl specify maxillary identity of NB6-4 lineages by repressing <i>CycE</i>.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869589"], "description"=>"<p>(A) Schematic representation of the average mRNA expression domains (in % of whole egg length, EL) of the Hox genes <i>labial</i> (<i>lab</i>), <i>Deformed</i> (<i>Dfd</i>), <i>Sex combs reduced</i> (<i>Scr</i>) and <i>Antennapedia</i> (<i>Antp</i>) in stage 6, 7 and 8. For original staining see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005961#pgen.1005961.s003\" target=\"_blank\">S3 Fig</a>. (B) Double <i>in-situ</i> hybridization to visualize expression pattern of <i>lab</i> (blue) and <i>Dfd</i>-mRNAs (red) at stage 5l to 9. No co-expression can be observed. Anterior to the left. Dashed line marks the ventral midline. (C) Antibody staining in the maxillary segment to visualize the protein expression pattern of Lab (red) and Dfd (blue) in relation to the Engrailed (En, green) domain from which NB6-4 segregates. No co-expression can be observed in stage 8 or 9. Upper panel shows three successive focal planes of a lateral view (anterior up, ventral to the right) of a whole mount embryo (Z-axis from -20, -10 to 0 μm). Tc, tritocerebrum. Lower panel shows filet preparation (anterior up, ventral view). The dash-lined box indicate the En-positive domain, from which NB6-4 delaminates; no expression of Lab can be observed. (D) Dfd (red) and Scr (blue) are co-expressed in the maxillary NB6-4 (Eg, green); two-cell stage shown at late stage 11. (E) NB6-4 expresses Dfd (red) and Scr (blue) in the maxillary segment (yellow arrow head), whereas NB6-4 in the labial segment lacks both of them (white arrow head). (F) All cells of the NB6-4 lineage in the labial segment express Antp (magenta). T1, first thoracic segment. Scale bar is 10 μm.</p>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130171, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005961.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Expression_pattern_of_Hox_genes_in_embryonic_gnathal_segments_/3130171", "title"=>"Expression pattern of Hox genes in embryonic gnathal segments.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-03-25 05:40:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/4869451", "https://ndownloader.figshare.com/files/4869463", "https://ndownloader.figshare.com/files/4869472", "https://ndownloader.figshare.com/files/4869487", "https://ndownloader.figshare.com/files/4869490", "https://ndownloader.figshare.com/files/4869502", "https://ndownloader.figshare.com/files/4869508", "https://ndownloader.figshare.com/files/4869517"], "description"=>"<div><p>During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of <i>Drosophila</i>, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene <i>Deformed</i> (<i>Dfd</i>). Interestingly, however, it also requires a non-cell-autonomous function of <i>labial</i> and <i>Antennapedia</i> that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes <i>labial</i>, <i>Dfd</i>, <i>Sex combs reduced</i> and <i>Antennapedia</i>. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous <i>Dfd</i> pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress <i>CyclinE</i> (<i>CycE</i>) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates <i>CycE</i> expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental patterning in the developing CNS.</p></div>", "links"=>[], "tags"=>["maxillary identity", "Hox genes", "receptor Neurotactin", "head region", "gnathal NBs", "function", "effector kinase Abelson tyrosine kinase", "Hippo effector Yorkie", "Hox Genes Specify Segmental Neuroblast Identity", "ground state", "Gnathal Region", "CycE expression", "pathway", "Embryonic CNS", "Hox gene Deformed", "gnathal segments", "Sex combs", "expression pattern", "molecule Amalgam"], "article_id"=>3130078, "categories"=>["Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Infectious Diseases"], "users"=>["Henrike Becker", "Simone Renner", "Gerhard M. Technau", "Christian Berger"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005961.s001", "https://dx.doi.org/10.1371/journal.pgen.1005961.s002", "https://dx.doi.org/10.1371/journal.pgen.1005961.s003", "https://dx.doi.org/10.1371/journal.pgen.1005961.s004", "https://dx.doi.org/10.1371/journal.pgen.1005961.s005", "https://dx.doi.org/10.1371/journal.pgen.1005961.s006", "https://dx.doi.org/10.1371/journal.pgen.1005961.s007", "https://dx.doi.org/10.1371/journal.pgen.1005961.s008"], "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Cell_Autonomous_and_Non_cell_autonomous_Function_of_Hox_Genes_Specify_Segmental_Neuroblast_Identity_in_the_Gnathal_Region_of_the_Embryonic_CNS_in_i_Drosophila_i_/3130078", "title"=>"Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in <i>Drosophila</i>", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-03-25 05:40:14"}

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{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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