{"id":14,"date":"2020-06-22T11:33:35","date_gmt":"2020-06-22T11:33:35","guid":{"rendered":"https:\/\/www.embl.org\/groups\/rapti\/home\/"},"modified":"2023-02-13T13:31:22","modified_gmt":"2023-02-13T13:31:22","slug":"home","status":"publish","type":"page","link":"https:\/\/www.embl.org\/groups\/rapti\/","title":{"rendered":"Home"},"content":{"rendered":"<div class=\"vf-grid vf-grid__col-3 | vf-u-margin__bottom--800\">\n      <div class=\"vf-grid__col--span-2\">\n      <div class=\"vf-content-hub-html\">\n  <!-- Generated by: http:\/\/content.embl.org\/api\/v1\/pattern.html?filter-content-type=profiles&amp;filter-uuid=4240a735-c64a-4998-9213-5e11d0d995b4&amp;pattern=node-teaser -->\n      <div data-embl-js-conditional-edit=\"28652\">\n              <h1 class=\"vf-lede\">The Rapti group dissects cellular and molecular mechanisms of nervous system assembly and the underlying glia\u2013neuron crosstalk, using advanced genetics, genomics and live imaging approaches.<\/p>\r\n\n            <a class=\"vf-text vf-text--body-r vf-link embl-conditional-edit\" rel=\"noopener noreferrer nofollow\" href=\"\/node\/28652\" target=\"_blank\">Edit<\/a>\n    <\/div>\n  <\/div>\n    <\/div>\n      <div >\n\n<!-- <style>\n  .vf-content-hub-html {\n    --vf-stack-margin--custom: unset !important;\n  }\n<\/style> -->\n\n    <div class=\"vf-content-hub-html vf-stack vf-stack--600\" data-cache=\"56ec340f\">\n      <!-- Generated by: http:\/\/content.embl.org\/api\/v1\/pattern.html?filter-content-type=person&amp;filter-field-value%5Bfield_person_positions.entity.field_position_membership%5D=leader&amp;filter-field-value%5Bfield_person_positions.entity.field_position_team.entity.field_foreignid%5D=531&amp;filter-ref-entity%5Bfield_person_positions%5D%5Btitle%5D=&amp;filter-ref-entity%5Bfield_person_positions%5D%5Bfield_position_primary%5D=1&amp;hide%5Bteam%2Cmobile%2Cphones%5D=1&amp;limit=5&amp;pattern=vf-profile-inline&amp;sort-field-value%5Bchanged%5D=DESC -->\n                \n                            <article class=\"vf-profile vf-profile--very-easy vf-profile--medium vf-profile--inline\" data-embl-js-conditional-edit=\"88754\">\n              <img decoding=\"async\" class=\"vf-profile__image\" src=\"https:\/\/content.embl.org\/\/sites\/default\/files\/styles\/medium\/public\/persons\/CP-60031928.jpg?itok=xZj1POJB\" alt=\"image of Georgia Rapti\" \/>\n      \n              <h3 class=\"vf-profile__title\">\n                      <a href=\"https:\/\/www.embl.org\/people\/person\/georgia-rapti\" class=\"vf-profile__link\">Georgia Rapti<\/a>\n                  <\/h3>\n      \n              <p class=\"vf-profile__job-title\">\n          Group Leader (Outgoing)\n        <\/p>\n      \n      \n      \n      \n      \n      \n              <p class=\"vf-profile__uuid\">\n          <span>ORCID:<\/span>\n          <a class=\"vf-profile__link vf-profile__link--secondary\" href=\"https:\/\/europepmc.org\/authors\/0000-0003-4836-8640\">\n            0000-0003-4836-8640\n          <\/a>\n        <\/p>\n            <a class=\"vf-text vf-text--body-r vf-link embl-conditional-edit\" rel=\"noopener noreferrer nofollow\" href=\"\/node\/88754\/88754\" target=\"_blank\">\n        Edit\n      <\/a>\n    <\/article>\n  <\/div>\n\n  <\/div>\n<\/div>\n\n\n\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<h3 class=\"wp-block-heading\">Previous and current research<\/h3>\n\n\n\n<h4 class=\"wp-block-heading\">How does the nervous system architecture assemble <em>in vivo<\/em>, in space and time?<\/h4>\n\n\n\n<p>Throughout an embryos\u2019 life, cells with diverse fates and morphologies interact to give rise to well-defined tissue architecture. The early assembly of nervous system circuits is fundamental for life and behavior; yet dissecting the events initiating this assembly is a tantalising challenge. How do nervous system cells interact spatio-temporally while concurrently diversifying their fates? Pioneer cells are thought to initiate circuit assembly, but their molecular identity, development, and interactions remain elusive. How do circuit components establish their specialised morphologies to coordinate assembly<em> in vivo<\/em>, towards functional connectivity? What interactions ensure the fidelity with which the mature nervous system structure is maintained? Which overarching principles pattern assembly across species?<\/p>\n\n\n\n<p>To address these questions, we employ an interdisciplinary line of real-time <em>in vivo<\/em> imaging and refined genetics, genomics, and molecular approaches. We will combine cellular and molecular studies with high-resolution imaging and omics approaches, in collaboration with fellow research groups. The main system we study is the nematode <em>C. elegans. <\/em>This is a valuable system for our interdisciplinary approach, since <em>C. elegans<\/em> has transparent embryos, traceable lineages, morphogenesis that is tractable at single-cell resolution, mapped nervous system anatomy and connectivity, a sequenced genome, and sophisticated genetics (see figure and videos). Many <em>C. elegans <\/em>neural cell types and genes are shared across invertebrate and vertebrate species. Thus, discovery of gene\u2013function relationships and the dissection of nervous system assembly in <em>C. elegans<\/em> is our route to addressing \u2013 in collaboration with other research groups \u2013 conserved principles in other organisms.<\/p>\n\n\n\n<p>Centralised nervous systems consist mainly of neurons and glia \u2013 lineally related cell types in about equal numbers. Neurons transmit electrical currents, while glia were long thought to passively support neurons\u2019 nutrition. However, glia were recently implicated in nervous system development and function, in physiology and pathology. We identified that <em>C. elegans <\/em>glia, similar to vertebrate glia, initiate hierarchical brain assembly: pioneer neurons and glia of specific molecular signature that cooperate functionally drive circuit assembly, they grow coalescing processes and molecularly guide circuit components (Figure 1). A set of diverse, conserved molecular cues drive circuit assembly synergistically through a glia\u2013neuron crosstalk that we are only beginning to understand. To dissect dynamic circuit assembly at the cellular and molecular levels, we investigate normal and defective development of the nervous system from the level of single neurons or glial cells to the scale of multicellular circuits (Fig.1). We can then trace back the emergence of circuits in real time (Figure 1, movies 1-2).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Future projects and goals<\/h3>\n\n\n\n<p>We map molecular and cellular interactions driving circuit architecture <em>in vivo<\/em> by dissecting:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Which factors establish identities of brain pioneer cells .<\/li>\n\n\n\n<li>How distinct cell identities &amp; interactions drive pioneer morphogenesis.<\/li>\n\n\n\n<li>How neuron\u2013glia crosstalk synergistically guides circuit assembly, to shape functional connectivity.<\/li>\n\n\n\n<li>Which cues drive communication of pioneer neurons and glia with neighboring cells and the extracellular matrix.<\/li>\n\n\n\n<li>Which overarching molecular and cellular principles of circuit assembly are shared across species.<\/li>\n\n\n\n<li>Which mechanisms control maintenance of glia &amp; neuron integrity.<\/li>\n<\/ul>\n\n\n\n<figure class=\"vf-figure wp-block-video\"><video style=\"max-width: 100%;\" controls src=\"https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/video1-rapti-group.mp4\"><\/video><figcaption class=\"vf-figure__caption\"><strong>Video 1:<\/strong>&nbsp;Pioneer axons grow and navigate to form the first bundle and initiate brain-circuit assembly&nbsp;<em>in vivo<\/em> (embryo, left). Proteins important for assembly can dynamically localize in the circuit (embryo, right). We investigate <em>in vivo<\/em> brain morphogenesis utilizing <em>in vivo<\/em> timelapse imaging in developing&nbsp;<em>C. elegans<\/em>&nbsp;embryos (left: pioneer axons in red, cell nuclei in green; right: adhesion protein in green).<\/figcaption><\/figure>\n\n\n\n<figure class=\"vf-figure wp-block-video\"><video style=\"max-width: 100%;\" controls src=\"https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/video2-rapti-group.mp4\"><\/video><figcaption class=\"vf-figure__caption\"><strong>Video 2:<\/strong> C. elegans animals of different developmental stages forage by a characteristic crawling locomotion. Genetic mutants with defective brain circuit show abnormal locomotion compared to wild-type animals. Mechanisms of circuit formation are ultimately key for proper nervous system function.<\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n\n\n<div class=\"\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><a href=\"https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/figure1-rapti-group.png\"><img loading=\"lazy\" decoding=\"async\" width=\"626\" height=\"1024\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/figure1-rapti-group-626x1024.png\" alt=\"Figure 1. The C. elegans brain circuit is formed by coalescing neurons and glia, organized in a circumferential ring\" class=\"wp-image-202\" srcset=\"https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/figure1-rapti-group-626x1024.png 626w, https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/figure1-rapti-group-183x300.png 183w, https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/figure1-rapti-group-768x1257.png 768w, https:\/\/www.embl.org\/groups\/rapti\/wp-content\/uploads\/2021\/05\/figure1-rapti-group.png 782w\" sizes=\"auto, (max-width: 626px) 100vw, 626px\" \/><\/a><figcaption class=\"vf-figure__caption\">Figure 1. The C. elegans brain circuit is formed by coalescing neurons and glia, organized in a circumferential ring (A. lateral view, B. section). Circuit structure is abnormal when disrupting signaling pathways that involve pioneer neurons and glia (B) or when morphogenesis of pioneer axons and glia is disrupted (C-F) (Rapti et al, 2017 &amp; our unpublished data). Brain circuit assembly is initiated by pioneer glia and axons coalescing and cooperating to guide follower axons (G,H). A cellular and molecular hierarchy underlying a precise glia-neuron crosstalk (I) drives brain assembly in developing embryos (J, and video 1). To dissect mechanisms of assembly and the crosstalk of brain components we study the development of pioneer neurons and glia (C-F), and their interactions (I), utilizing advanced genetics and genomics, single-cell resolution in vivo imaging (C-F) and high-resolution imaging of the entire circuit (B). The array of molecular signals that drive glia-neuron interactions include many conserved genes and our gene-function analysis may uncover conserved glia\u2013neuron crosstalk.<\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"embl_taxonomy":[],"class_list":["post-14","page","type-page","status-publish","hentry"],"acf":[],"embl_taxonomy_terms":[],"_links":{"self":[{"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/pages\/14","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/comments?post=14"}],"version-history":[{"count":11,"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/pages\/14\/revisions"}],"predecessor-version":[{"id":4924,"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/pages\/14\/revisions\/4924"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/media?parent=14"}],"wp:term":[{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/rapti\/wp-json\/wp\/v2\/embl_taxonomy?post=14"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}