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The Unc-5 Receptor Is Directly Regulated by Tinman in the Developing Drosophila Dorsal Vessel
During early heart morphogenesis cardiac cells migrate in two bilateral opposing rows, meet at the dorsal midline and fuse to form a hollow tube known as the primary heart field in vertebrates or dorsal vessel (DV) in Drosophila. Guidance receptors are thought to mediate this evolutionarily conserve...
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Published in: | PloS one 2015-09, Vol.10 (9), p.e0137688-e0137688 |
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description | During early heart morphogenesis cardiac cells migrate in two bilateral opposing rows, meet at the dorsal midline and fuse to form a hollow tube known as the primary heart field in vertebrates or dorsal vessel (DV) in Drosophila. Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown. In our work, we demonstrate how Tinman (Tin), the Drosophila homolog of the Nkx-2.5 transcription factor, regulates the Unc-5 receptor during DV tube morphogenesis. We use genetics, expression analysis with single cell mRNA resolution and enhancer-reporter assays in vitro or in vivo to demonstrate that Tin is required for Unc-5 receptor expression specifically in cardioblasts. We show that Tin can bind to evolutionary conserved sites within an Unc-5 DV enhancer and that these sites are required for Tin-dependent transactivation both in vitro and in vivo. |
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Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown. In our work, we demonstrate how Tinman (Tin), the Drosophila homolog of the Nkx-2.5 transcription factor, regulates the Unc-5 receptor during DV tube morphogenesis. We use genetics, expression analysis with single cell mRNA resolution and enhancer-reporter assays in vitro or in vivo to demonstrate that Tin is required for Unc-5 receptor expression specifically in cardioblasts. We show that Tin can bind to evolutionary conserved sites within an Unc-5 DV enhancer and that these sites are required for Tin-dependent transactivation both in vitro and in vivo.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0137688</identifier><identifier>PMID: 26356221</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Base Sequence ; Binding Sites ; Cell migration ; Cell receptors ; Drosophila ; Drosophila - embryology ; Drosophila - genetics ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Enhancer Elements, Genetic ; Evolutionary conservation ; Gene Expression ; Gene Expression Regulation, Developmental ; Gene regulation ; Genes ; Genes, Reporter ; Genetic aspects ; Genetics ; Heart ; Heart - embryology ; Heart diseases ; Homology ; Insects ; Invertebrates ; Laboratories ; Microprocessors ; Morphogenesis ; Myoblasts, Cardiac - metabolism ; Neurosciences ; Nkx2.5 protein ; Nucleotide Motifs ; Organogenesis ; Pathology ; Physiological aspects ; Protein Binding ; Receptors ; Repressor Proteins - metabolism ; Sequence Alignment ; Trans-Activators - metabolism ; Transcription factors ; Vertebrates</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0137688-e0137688</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Asadzadeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Asadzadeh et al 2015 Asadzadeh et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3e0bc7ef43b39523671eded9675e32f646bdb04f8a88d5e68b664f19b30d103a3</citedby><cites>FETCH-LOGICAL-c692t-3e0bc7ef43b39523671eded9675e32f646bdb04f8a88d5e68b664f19b30d103a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1710982774/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1710982774?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26356221$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Giniger, Edward</contributor><creatorcontrib>Asadzadeh, Jamshid</creatorcontrib><creatorcontrib>Neligan, Niamh</creatorcontrib><creatorcontrib>Canabal-Alvear, Judith J</creatorcontrib><creatorcontrib>Daly, Amanda C</creatorcontrib><creatorcontrib>Kramer, Sunita Gupta</creatorcontrib><creatorcontrib>Labrador, Juan-Pablo</creatorcontrib><title>The Unc-5 Receptor Is Directly Regulated by Tinman in the Developing Drosophila Dorsal Vessel</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>During early heart morphogenesis cardiac cells migrate in two bilateral opposing rows, meet at the dorsal midline and fuse to form a hollow tube known as the primary heart field in vertebrates or dorsal vessel (DV) in Drosophila. Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown. In our work, we demonstrate how Tinman (Tin), the Drosophila homolog of the Nkx-2.5 transcription factor, regulates the Unc-5 receptor during DV tube morphogenesis. We use genetics, expression analysis with single cell mRNA resolution and enhancer-reporter assays in vitro or in vivo to demonstrate that Tin is required for Unc-5 receptor expression specifically in cardioblasts. We show that Tin can bind to evolutionary conserved sites within an Unc-5 DV enhancer and that these sites are required for Tin-dependent transactivation both in vitro and in vivo.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Cell migration</subject><subject>Cell receptors</subject><subject>Drosophila</subject><subject>Drosophila - embryology</subject><subject>Drosophila - genetics</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Enhancer Elements, Genetic</subject><subject>Evolutionary conservation</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genes, Reporter</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Heart</subject><subject>Heart - embryology</subject><subject>Heart diseases</subject><subject>Homology</subject><subject>Insects</subject><subject>Invertebrates</subject><subject>Laboratories</subject><subject>Microprocessors</subject><subject>Morphogenesis</subject><subject>Myoblasts, Cardiac - 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Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown. In our work, we demonstrate how Tinman (Tin), the Drosophila homolog of the Nkx-2.5 transcription factor, regulates the Unc-5 receptor during DV tube morphogenesis. We use genetics, expression analysis with single cell mRNA resolution and enhancer-reporter assays in vitro or in vivo to demonstrate that Tin is required for Unc-5 receptor expression specifically in cardioblasts. We show that Tin can bind to evolutionary conserved sites within an Unc-5 DV enhancer and that these sites are required for Tin-dependent transactivation both in vitro and in vivo.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26356221</pmid><doi>10.1371/journal.pone.0137688</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Base Sequence Binding Sites Cell migration Cell receptors Drosophila Drosophila - embryology Drosophila - genetics Drosophila Proteins - genetics Drosophila Proteins - metabolism Enhancer Elements, Genetic Evolutionary conservation Gene Expression Gene Expression Regulation, Developmental Gene regulation Genes Genes, Reporter Genetic aspects Genetics Heart Heart - embryology Heart diseases Homology Insects Invertebrates Laboratories Microprocessors Morphogenesis Myoblasts, Cardiac - metabolism Neurosciences Nkx2.5 protein Nucleotide Motifs Organogenesis Pathology Physiological aspects Protein Binding Receptors Repressor Proteins - metabolism Sequence Alignment Trans-Activators - metabolism Transcription factors Vertebrates |
title | The Unc-5 Receptor Is Directly Regulated by Tinman in the Developing Drosophila Dorsal Vessel |
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