Une \u00e9tude publi\u00e9e dans la revue scientifique Science Advances par l\u2019\u00e9quipe de Sigol\u00e8ne Meilhac (Inserm, Institut Imagine, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9) remet en cause le mod\u00e8le dominant expliquant la cr\u00e9ation de l\u2019asym\u00e9trie gauche\u2011droite des organes au cours du d\u00e9veloppement embryonnaire. Jusqu\u2019\u00e0 pr\u00e9sent, un consensus s\u2019\u00e9tait \u00e9tabli depuis la fin des ann\u00e9es 1990 autour d\u2019un m\u00e9canisme fond\u00e9 sur l\u2019action de cils situ\u00e9s dans une petite cavit\u00e9 embryonnaire appel\u00e9e \u00ab n\u0153ud \u00bb. Le mouvement rotatif de ces cils cr\u00e9e un courant de liquide orient\u00e9 vers la gauche, cens\u00e9 d\u00e9clencher une cascade mol\u00e9culaire domin\u00e9e par le g\u00e8ne Nodal, d\u00e9finissant le c\u00f4t\u00e9 gauche de l\u2019embryon. Ce n\u0153ud \u00e9tait qualifi\u00e9 \u00ab d\u2019organisateur gauche\u2011droite \u00bb selon le principe \u00ab pas de courant, pas d\u2019asym\u00e9trie \u00bb.<\/p>\n
Les chercheurs ont \u00e9tudi\u00e9 un mod\u00e8le murin porteur d\u2019une mutation du g\u00e8ne Ccdc40, qui paralyse ces cils. Chez l\u2019\u00eatre humain, Ccdc40 est le troisi\u00e8me g\u00e8ne le plus fr\u00e9quemment impliqu\u00e9 dans la dyskin\u00e9sie ciliaire primitive, maladie rare associant des troubles respiratoires chroniques, une infertilit\u00e9 et, chez certains patients, une disposition en miroir des organes internes. Dans ce mod\u00e8le, l\u2019\u00e9quipe a confirm\u00e9, par microscopie \u00e9lectronique et par observation de microbilles fluorescentes dans le n\u0153ud, l\u2019absence totale de mouvement ciliaire et de courant de liquide chez tous les animaux \u00e9tudi\u00e9s.<\/p>\n
Contrairement au mod\u00e8le th\u00e9orique, la suppression du courant n\u2019a pas entra\u00een\u00e9 le d\u00e9sordre g\u00e9n\u00e9ralis\u00e9 attendu dans l\u2019orientation des organes. La reconstitution en trois dimensions, organe par organe, de l\u2019anatomie des souriceaux \u00e0 la naissance a montr\u00e9 que, dans une majorit\u00e9 de cas (70 % des animaux, valeur mentionn\u00e9e mais non compl\u00e9t\u00e9e dans le texte), l\u2019organisation gauche\u2011droite demeurait globalement coh\u00e9rente. Les auteurs concluent que le courant ciliaire ne g\u00e9n\u00e8re pas, \u00e0 lui seul, l\u2019asym\u00e9trie, mais qu\u2019il en oriente seulement le sens. Ils mettent en \u00e9vidence l\u2019existence d\u2019un second m\u00e9canisme, jusqu\u2019ici non identifi\u00e9, impliquant la voie de signalisation cellulaire WNT, qui compl\u00e8te ce dispositif.<\/p>\n
Ces travaux concernent la compr\u00e9hension de l\u2019h\u00e9t\u00e9rotaxie, maladie rare du d\u00e9veloppement caract\u00e9ris\u00e9e par une orientation discordante des organes internes, touchant environ une naissance sur 10 000 et associ\u00e9e dans la majorit\u00e9 des cas \u00e0 des malformations cardiaques graves, responsables du pronostic vital plus que la position des organes elle\u2011m\u00eame. Actuellement, une cause g\u00e9n\u00e9tique n\u2019est identifi\u00e9e que chez un patient sur cinq. Les r\u00e9sultats publi\u00e9s contribuent \u00e0 pr\u00e9ciser les m\u00e9canismes de mise en place de l\u2019asym\u00e9trie gauche\u2011droite et pourraient, \u00e0 terme, \u00e9clairer l\u2019identification de nouvelles causes g\u00e9n\u00e9tiques et la compr\u00e9hension de certaines pathologies rares li\u00e9es aux cils et aux anomalies de position des organes. Les implications cliniques ou en termes de prise en charge ne sont toutefois pas d\u00e9taill\u00e9es dans le texte, et les r\u00e9sultats demeurent pour l\u2019instant limit\u00e9s \u00e0 un mod\u00e8le murin.\u00a0(contenu r\u00e9sum\u00e9 par l’IA)\u200bLire la Suite<\/a>\u200b<\/p>","protected":false},"excerpt":{"rendered":" Une \u00e9tude publi\u00e9e dans la revue scientifique Science Advances par l\u2019\u00e9quipe de Sigol\u00e8ne Meilhac (Inserm, Institut Imagine, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9) remet en cause le mod\u00e8le dominant expliquant la […]<\/p>\n","protected":false},"author":1,"featured_media":4209,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[3],"tags":[68,227],"class_list":["post-18086","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sante-publique-prevention-epidemiologie","tag-inserm","tag-ia"],"_links":{"self":[{"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=\/wp\/v2\/posts\/18086","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=18086"}],"version-history":[{"count":0,"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=\/wp\/v2\/posts\/18086\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=\/wp\/v2\/media\/4209"}],"wp:attachment":[{"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=18086"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=18086"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/veilles-affaires-sociales.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=18086"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}