Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans
Terminal differentiation generates the specialized features and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called 'terminal selectors' that directly activate a set of downstream e...
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Veröffentlicht in: | Development (Cambridge) 2018-11, Vol.145 (22) |
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creator | Zheng, Chaogu Jin, Felix Qiaochu Trippe, Brian Loeber Wu, Ji Chalfie, Martin |
description | Terminal differentiation generates the specialized features and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called 'terminal selectors' that directly activate a set of downstream effector genes. In
, the differentiation of both the mechanosensory touch receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons uses the terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes, however, because a complex of two transcriptional repressors (EGL-44/EGL-46) prevents their expression. Here, we show that the ZEB family transcriptional factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by preventing the expression of EGL-44/EGL-46. As EGL-44/EGL-46 also inhibits the production of ZAG-1, these proteins form a bistable, negative-feedback loop that regulates the choice between the two neuronal fates. |
doi_str_mv | 10.1242/dev.168096 |
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, the differentiation of both the mechanosensory touch receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons uses the terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes, however, because a complex of two transcriptional repressors (EGL-44/EGL-46) prevents their expression. Here, we show that the ZEB family transcriptional factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by preventing the expression of EGL-44/EGL-46. As EGL-44/EGL-46 also inhibits the production of ZAG-1, these proteins form a bistable, negative-feedback loop that regulates the choice between the two neuronal fates.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Biomarkers - metabolism</subject><subject>Caenorhabditis elegans - cytology</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Caenorhabditis elegans - metabolism</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Models, Biological</subject><subject>Mutation - genetics</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Penetrance</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>RNA Interference</subject><subject>Time Factors</subject><subject>Touch - physiology</subject><subject>Transcription Factors - metabolism</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1r3DAQFaWl2aS99AcEHUvBiT68tnQphKVtAoFc2rMYS6NYwSttJXsh_z5aNgnJSYPmvTcz7xHyjbMLLlpx6XB_wTvFdPeBrHjb943mQn8kK6bXrOFa8xNyWsoDY0x2ff-ZnEgmNOedWJH9TRzDEOaQIk2eWpwm6mFGmnGXsZSUCy1ol1rTeUTqgveYMc4BXjiH7zktdqwci7s5ZRpxySmWQ3cDGFMeYXB1SKE44T3E8oV88jAV_Pr8npF_v3_93Vw3t3d_bjZXt42VvZob21Ues-CwdWtl1TCAlNxr5gG9BNeCwtYq54T2a1Raq3q5h1Y7B5YpIc_Iz6Pubhm26GxdPMNkdjlsIT-aBMG878Qwmvu0N53oRK9ZFfj-LJDT_wXLbLahHFyCiGkpRlQbVbVc8gr9cYTanErJ6F_HcGYOQZkalDkGVcHnbxd7hb4kI58A9GmT6w</recordid><startdate>20181115</startdate><enddate>20181115</enddate><creator>Zheng, Chaogu</creator><creator>Jin, Felix Qiaochu</creator><creator>Trippe, Brian Loeber</creator><creator>Wu, Ji</creator><creator>Chalfie, Martin</creator><general>The Company of Biologists Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5048-4520</orcidid><orcidid>https://orcid.org/0000-0002-9079-7046</orcidid></search><sort><creationdate>20181115</creationdate><title>Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans</title><author>Zheng, Chaogu ; Jin, Felix Qiaochu ; Trippe, Brian Loeber ; Wu, Ji ; Chalfie, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-c6abd0cade4d58c8bba331f90faef3ad4a8e4c8dd29f5e8998912fa49ddac0823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Biomarkers - metabolism</topic><topic>Caenorhabditis elegans - cytology</topic><topic>Caenorhabditis elegans - genetics</topic><topic>Caenorhabditis elegans - metabolism</topic><topic>Caenorhabditis elegans Proteins - metabolism</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Models, Biological</topic><topic>Mutation - genetics</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Penetrance</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>RNA Interference</topic><topic>Time Factors</topic><topic>Touch - physiology</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zheng, Chaogu</creatorcontrib><creatorcontrib>Jin, Felix Qiaochu</creatorcontrib><creatorcontrib>Trippe, Brian Loeber</creatorcontrib><creatorcontrib>Wu, Ji</creatorcontrib><creatorcontrib>Chalfie, Martin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zheng, Chaogu</au><au>Jin, Felix Qiaochu</au><au>Trippe, Brian Loeber</au><au>Wu, Ji</au><au>Chalfie, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2018-11-15</date><risdate>2018</risdate><volume>145</volume><issue>22</issue><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>Terminal differentiation generates the specialized features and functions that allow postmitotic cells to acquire their distinguishing characteristics. 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, the differentiation of both the mechanosensory touch receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons uses the terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes, however, because a complex of two transcriptional repressors (EGL-44/EGL-46) prevents their expression. Here, we show that the ZEB family transcriptional factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by preventing the expression of EGL-44/EGL-46. As EGL-44/EGL-46 also inhibits the production of ZAG-1, these proteins form a bistable, negative-feedback loop that regulates the choice between the two neuronal fates.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>30291162</pmid><doi>10.1242/dev.168096</doi><orcidid>https://orcid.org/0000-0002-5048-4520</orcidid><orcidid>https://orcid.org/0000-0002-9079-7046</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Base Sequence Biomarkers - metabolism Caenorhabditis elegans - cytology Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism Caenorhabditis elegans Proteins - metabolism Cell Differentiation Cell Lineage Gene Expression Regulation, Developmental Models, Biological Mutation - genetics Neurons - cytology Neurons - metabolism Penetrance Receptors, Cell Surface - metabolism RNA Interference Time Factors Touch - physiology Transcription Factors - metabolism |
title | Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans |
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