{"id":58,"date":"2018-07-06T09:21:23","date_gmt":"2018-07-06T16:21:23","guid":{"rendered":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/?page_id=58"},"modified":"2018-08-04T13:10:04","modified_gmt":"2018-08-04T20:10:04","slug":"the-role-of-smades-in-endocardial-cushion-development","status":"publish","type":"page","link":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/the-role-of-smades-in-endocardial-cushion-development\/","title":{"rendered":"Hemogenic endocardium"},"content":{"rendered":"<h1>Under construction<\/h1>\n<h2><strong>The Role of Smades in Endocardial Cushion Development<\/strong><\/h2>\n<p>Within the cytoplasm of BMP and TGF-\u00df receiving cells, Smad6 and Smad7 act as signal attenuators by interfering with Smad4 dependent signal transduction.\u00a0 These inhibitory Smads (iSmads) are structurally similar to other Smad proteins, but lack a C-terminal phosphorylation motif (Whitman 1997).\u00a0 <em>Smad6<\/em>\u00a0mutants on a mixed genetic background exhibit adult outflow tract defects including advanced ossification and cartilaginous metaplasia of the aortic media.\u00a0 The valves of adult mutants also exhibit striking valve hyperplasticity.\u00a0 Given that\u00a0<em>Smad6<\/em>\u00a0is expressed within the endocardial cushions early in heart development it could play an active role in regulating the number of endocardial cells that undergo EMT and maintaining the proper developmental window in which EMT can occur.\u00a0 Smad6 expression is also maintained throughout development (Galvin et al., 2000), indicating the possibility that it is involved in regulating mesenchymal cell proliferation during valve formation and remodeling.\u00a0 Further, a recent study in the zebrafish model suggests a possible Smad6-mediated mechanism of SHF-progenitor differentiation in the outflow tract (de Pater et al., 2012).\u00a0 However, this has not been addressed within a murine model and could relate to BMP associated congenital OFT defects.\u00a0 We are currently using a global Smad6 knockout allele bred onto a congenic C57\/Bl6 genetic background to investigate the role this iSmad plays embryonically in regulating outflow tract and endocardial development. Our initial results show that on a strict congenic background Smad6 knockout results in embryonic valve hyperplasia as early as E12.5.\u00a0 Smad6 mutants also exhibit novel embryonic congenital defects including double outlet right ventricle.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-59 alignnone\" src=\"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-content\/uploads\/sites\/181\/2018\/07\/SMAD_ISH_Figure_copy.jpg\" alt=\"\" width=\"853\" height=\"1065\" \/><\/p>\n<p><strong>Expression of iSmads during early cardiac development.<\/strong><\/p>\n<p>In situ hybridization of transverse sections from E10.5 (A-G) and E9.5 (H,I) wildtype embryos.\u00a0\u00a0 <em>Smad6<\/em> and <em>Smad7<\/em> have a shared expression domain within both cushion endocardium and mesenchyme of the atrioventricular canal (A,B) and outflow tract (B,C).\u00a0 <em>Smad6<\/em> expression co-localizes with the SHF marker <em>Isl1<\/em> within the pharyngeal mesoderm (E,F, arrowheads), but not within distal populations of SHF progenitors (E,F, arrows).\u00a0 Control sense reaction demonstrates hybridization specificity (G).\u00a0 <em>Smad6<\/em> expression co-localizes with the SHF-marker <em>Isl1<\/em> within distal OFT myocardium (H,I, bracket).\u00a0 a \u2013 atria, e \u2013 endcardium, lv \u2013 left ventricle, m \u2013 myocardium, rv \u2013 right ventricle.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Under construction The Role of Smades in Endocardial Cushion Development Within the cytoplasm of BMP and TGF-\u00df receiving cells, Smad6 and Smad7 act as signal attenuators by interfering with Smad4 &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/the-role-of-smades-in-endocardial-cushion-development\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Hemogenic endocardium&#8221;<\/span><\/a><\/p>\n","protected":false},"author":4,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-58","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/pages\/58","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/comments?post=58"}],"version-history":[{"count":4,"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/pages\/58\/revisions"}],"predecessor-version":[{"id":261,"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/pages\/58\/revisions\/261"}],"wp:attachment":[{"href":"https:\/\/sites.lifesci.ucla.edu\/mcdb-nakanolab2\/wp-json\/wp\/v2\/media?parent=58"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}