{"id":11,"date":"2019-03-25T10:17:00","date_gmt":"2019-03-25T10:17:00","guid":{"rendered":"http:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/?page_id=11"},"modified":"2026-03-04T10:30:59","modified_gmt":"2026-03-04T10:30:59","slug":"the-drosophila-embryonic-midgut-as-a-paradigm-for-inductive-signalling","status":"publish","type":"page","link":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/research-past-and-present\/the-drosophila-embryonic-midgut-as-a-paradigm-for-inductive-signalling\/","title":{"rendered":"Inductive signalling in the Drosophila embryonic midgut"},"content":{"rendered":"\n<p>Early on, we discovered a discrete midgut-specific enhancer upstream of the&nbsp;<em>Ultrabithorax<\/em>&nbsp;promoter whose control was distinct from that of the epidermis-specific enhancers and silencers. This enhancer mediates position-specific activation of&nbsp;<em>Ultrabithorax<\/em>&nbsp;in a single segment-wide stripe in an internal mesodermal layer of the embryo \u2013 the visceral mesoderm that envelops the embryonic midgut. Its minimal ~240bp core element turned out to be responsive to positional signalling from adjacent cells secreting Wingless\/Wnt, Dpp\/TGFbeta and Vein\/Neuregulin (whereby the first term denotes the fly founder protein, followed by its mammalian ortholog; here and below). We thus discovered how the HOX gene&nbsp;<em>Ultrabithorax<\/em>&nbsp;maintains itself in the visceral mesoderm via an indirect autoregulatory loop through autocrine Dpp and Vein signalling and paracrine Wingless signalling from neighbouring cell groups. This ensures coordinate maintenance of&nbsp;<em>Ultrabithorax&nbsp;<\/em>expression in all cells that make up the segmental stripe surrounding the midgut. Positional inputs from these signals synergise at, and are integrated by, the&nbsp;<em>Ultrabithorax&nbsp;<\/em>midgut enhancer.&nbsp;<\/p>\n\n\n\n<p>The same three signals cross over to the underlying endodermal cell layer, to specify a single stripe of Labial expression opposite the Ultrabithorax stripe though an intermediate endodermal target gene Dfos (<em>Drosophila<\/em>c-Fos). As in the case of&nbsp;<em>Ultrabithorax<\/em>, their inputs are integrated by a compact enhancer upstream of&nbsp;<em>labial<\/em>. Notably, Wingless signalling determines a gradient of Labial expression throughout the stripe, whereby the highest Labial levels are nearest to the Wingless signalling source. Subsequently, Labial specifies the differentiation of the so-called copper cells (a specialised cell type in the larval \u2018stomach\u2019) whereby the levels of Labial in these cells directly determines their size. These acid-secreting cells are required for larval growth, moulting and puparium formation. Through our work, the embryonic midgut became known as a paradigm for inductive signalling across two germ layers.&nbsp;<\/p>\n\n\n<style type=\"text\/css\">\n#foogallery-gallery-189.fg-justified .fg-item { margin-right: 20px; margin-bottom: 20px; }\n#foogallery-gallery-189.fg-justified .fg-image { height: 150px; }<\/style>\n\t\t\t<div class=\"foogallery foogallery-container foogallery-justified foogallery-lightbox-foobox fg-justified fg-ready fg-light fg-shadow-outline fg-loading-default fg-loaded-fade-in fg-caption-hover fg-hover-fade fg-hover-zoom\" id=\"foogallery-gallery-189\" data-foogallery=\"{&quot;item&quot;:{&quot;showCaptionTitle&quot;:true,&quot;showCaptionDescription&quot;:true},&quot;lazy&quot;:true,&quot;template&quot;:{&quot;rowHeight&quot;:150,&quot;maxRowHeight&quot;:225,&quot;margins&quot;:20,&quot;align&quot;:&quot;center&quot;,&quot;lastRow&quot;:&quot;smart&quot;}}\" style=\"--fg-title-line-clamp: 0; --fg-description-line-clamp: 0;\" >\n\t<div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide1-1.jpg\" data-caption-title=\"HOX gene expression in the visceral mesoderm of the embryonic midgut\" data-attachment-id=\"59\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"HOX gene expression in the visceral mesoderm of the embryonic midgut\" title=\"HOX gene expression in the visceral mesoderm of the embryonic midgut\" height=\"225\" width=\"214\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide1-1\/3074139894.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22214%22%20height%3D%22225%22%20viewBox%3D%220%200%20214%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">HOX gene expression in the visceral mesoderm of the embryonic midgut<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide2-1.jpg\" data-caption-title=\"Patterning of the midgut epithelium by signals from the visceral mesoderm\" data-attachment-id=\"60\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img fetchpriority=\"high\" decoding=\"async\" alt=\"Patterning of the midgut epithelium by signals from the visceral mesoderm\" title=\"Patterning of the midgut epithelium by signals from the visceral mesoderm\" height=\"225\" width=\"348\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide2-1\/3323702490.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22348%22%20height%3D%22225%22%20viewBox%3D%220%200%20348%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">Patterning of the midgut epithelium by signals from the visceral mesoderm<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide4-1.jpg\" data-caption-title=\"A parautocrine positive feedback loop ensuring coordinate expression of Ubx\" data-attachment-id=\"62\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"A parautocrine positive feedback loop ensuring coordinate expression of Ubx\" title=\"A parautocrine positive feedback loop ensuring coordinate expression of Ubx\" height=\"225\" width=\"232\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide4-1\/3253086986.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22232%22%20height%3D%22225%22%20viewBox%3D%220%200%20232%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">A parautocrine positive feedback loop ensuring coordinate expression of Ubx<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide5-1.jpg\" data-caption-title=\"An inductive cascade from Ubx to Labial mediated by multiple signals\" data-attachment-id=\"63\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"An inductive cascade from Ubx to Labial mediated by multiple signals\" title=\"An inductive cascade from Ubx to Labial mediated by multiple signals\" height=\"225\" width=\"288\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide5-1\/3337435359.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22288%22%20height%3D%22225%22%20viewBox%3D%220%200%20288%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">An inductive cascade from Ubx to Labial mediated by multiple signals<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide6-1.jpg\" data-caption-title=\"A Wingless-dependent gradient of Labial expression in the midgut epithelium\" data-attachment-id=\"64\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"A Wingless-dependent gradient of Labial expression in the midgut epithelium\" title=\"A Wingless-dependent gradient of Labial expression in the midgut epithelium\" height=\"225\" width=\"365\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide6-1\/3661095822.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22365%22%20height%3D%22225%22%20viewBox%3D%220%200%20365%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">A Wingless-dependent gradient of Labial expression in the midgut epithelium<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide7.jpg\" data-caption-title=\"Cell type specification in the larval gut depends on Wingless thresholds levels\" data-attachment-id=\"65\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"Cell type specification in the larval gut depends on Wingless thresholds levels\" title=\"Cell type specification in the larval gut depends on Wingless thresholds levels\" height=\"225\" width=\"466\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide7\/3698322105.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22466%22%20height%3D%22225%22%20viewBox%3D%220%200%20466%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">Cell type specification in the larval gut depends on Wingless thresholds levels<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide8.jpg\" data-caption-title=\"Copper cells are specified by Labial expression in the midgut epithelium\" data-attachment-id=\"66\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"Copper cells are specified by Labial expression in the midgut epithelium\" title=\"Copper cells are specified by Labial expression in the midgut epithelium\" height=\"225\" width=\"168\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide8\/581544665.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22168%22%20height%3D%22225%22%20viewBox%3D%220%200%20168%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">Copper cells are specified by Labial expression in the midgut epithelium<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><div class=\"fg-item fg-type-image fg-idle\"><figure class=\"fg-item-inner\"><a href=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/Slide9.jpg\" data-caption-title=\"Ubiquitous Wingless in the embryonic midgut specifies ectopic copper cells\" data-attachment-id=\"67\" data-type=\"image\" class=\"fg-thumb\"><span class=\"fg-image-wrap\"><img decoding=\"async\" alt=\"Ubiquitous Wingless in the embryonic midgut specifies ectopic copper cells\" title=\"Ubiquitous Wingless in the embryonic midgut specifies ectopic copper cells\" height=\"225\" width=\"239\" class=\"skip-lazy fg-image\" data-src-fg=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-content\/uploads\/sites\/23\/cache\/Slide9\/4083049475.jpg\" src=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%22http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%22%20width%3D%22239%22%20height%3D%22225%22%20viewBox%3D%220%200%20239%20225%22%3E%3C%2Fsvg%3E\" loading=\"eager\"><\/span><span class=\"fg-image-overlay\"><\/span><\/a><figcaption class=\"fg-caption\"><div class=\"fg-caption-inner\"><div class=\"fg-caption-title\">Ubiquitous Wingless in the embryonic midgut specifies ectopic copper cells<\/div><\/div><\/figcaption><\/figure><div class=\"fg-loader\"><\/div><\/div><\/div>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<details class=\"wp-block-details is-layout-flow wp-block-details-is-layout-flow\"><summary>Relevant references:<\/summary>\t\t<div class=\"lmb-publications-update-me pubmed-feed\">\n\t\t\t<pre style=\"display:none;\">{\"pubid\":\"2897631,2573526,2573527,1973634,8097881,7908470,7907275,7588630,7600572,8631263,9310330,9649506,9835654,11044608\",\"showAllPapers\":true,\"showAllAuthors\":true,\"pubmedOrOrcid\":\"pubmed\",\"pubmedApiKey\":\"a06f23aba62c0b6ba4feaeb0317dde9a7509\",\"transientExpireTime\":86400,\"pageBlockId\":\"ce142be8-4701-4aae-b0f8-a5199d5019f1\",\"showYearWhere\":\"yearafter\",\"enablePagination\":false,\"authorFormat\":\"abbreviated\",\"sortOrder\":\"oldest\"}<\/pre>\n\t\t<\/div>\n\t\t\n\n\n<ul class=\"wp-block-list\">\n<li><span class=\"pubAuthors\">Bienz, M.<\/span> <span class=\"pubDate\">(1996)<\/span><br><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1084952196900166\" class=\"pubLink\" target=\"_blank\" rel=\"noopener\">Induction of the endoderm in Drosophila.<\/a><br><span class=\"pubJournal\">Seminars Cell Develop Biol<\/span> <span class=\"pubJournalRef\"><strong>7<\/strong>113-119<\/span><\/li>\n<\/ul>\n<\/details>\n","protected":false},"excerpt":{"rendered":"<p>Early on, we discovered a discrete midgut-specific enhancer upstream of the&nbsp;Ultrabithorax&nbsp;promoter whose control was distinct from that of the epidermis-specific enhancers and silencers. This enhancer mediates position-specific activation of&nbsp;Ultrabithorax&nbsp;in a single segment-wide stripe in an internal mesodermal layer of the embryo \u2013 the visceral mesoderm that envelops the embryonic midgut. Its minimal ~240bp core element [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":138,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"class_list":{"0":"post-11","1":"page","2":"type-page","3":"status-publish","5":"entry"},"featured_image_src":null,"featured_image_src_square":null,"_links":{"self":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/pages\/11","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/comments?post=11"}],"version-history":[{"count":22,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/pages\/11\/revisions"}],"predecessor-version":[{"id":499,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/pages\/11\/revisions\/499"}],"up":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/pages\/138"}],"wp:attachment":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/bienz\/wp-json\/wp\/v2\/media?parent=11"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}