COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians
Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal i...
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description | Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals. |
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Aziz</contributor><creatorcontrib>Cowles, Martis W ; Omuro, Kerilyn C ; Stanley, Brianna N ; Quintanilla, Carlo G ; Zayas, Ricardo M ; Aboobaker, A. Aziz</creatorcontrib><description>Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1004746</identifier><identifier>PMID: 25356635</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Central Nervous System - growth & development ; Experiments ; Freshwater Biology ; Gene expression ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Genetic aspects ; Genotype & phenotype ; Hybridization ; Medicine and Health Sciences ; Messenger RNA ; Nervous system ; Neurons ; Neuropeptides ; Physiological aspects ; Planarians - genetics ; Planarians - growth & development ; Platyhelminthes ; Pluripotent Stem Cells ; Regeneration - genetics ; RNA Interference ; RNA, Messenger - genetics ; Stem cell research ; Stem cells ; Studies ; Transcription factors</subject><ispartof>PLoS genetics, 2014-10, Vol.10 (10), p.e1004746-e1004746</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Cowles et al 2014 Cowles et al</rights><rights>2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Cowles MW, Omuro KC, Stanley BN, Quintanilla CG, Zayas RM (2014) COE Loss-of-Function Analysis Reveals a Genetic Program Underlying Maintenance and Regeneration of the Nervous System in Planarians. PLoS Genet 10(10): e1004746. doi:10.1371/journal.pgen.1004746</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764t-be9e4c51132761171a40e4c7c16b4f27ebcc5917cf16b868e437e2247a2a31f73</citedby><cites>FETCH-LOGICAL-c764t-be9e4c51132761171a40e4c7c16b4f27ebcc5917cf16b868e437e2247a2a31f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214590/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214590/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25356635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Aboobaker, A. Aziz</contributor><creatorcontrib>Cowles, Martis W</creatorcontrib><creatorcontrib>Omuro, Kerilyn C</creatorcontrib><creatorcontrib>Stanley, Brianna N</creatorcontrib><creatorcontrib>Quintanilla, Carlo G</creatorcontrib><creatorcontrib>Zayas, Ricardo M</creatorcontrib><title>COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. 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Aziz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>10</volume><issue>10</issue><spage>e1004746</spage><epage>e1004746</epage><pages>e1004746-e1004746</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25356635</pmid><doi>10.1371/journal.pgen.1004746</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biology and Life Sciences Central Nervous System - growth & development Experiments Freshwater Biology Gene expression Gene Expression Regulation, Developmental Gene Knockdown Techniques Genetic aspects Genotype & phenotype Hybridization Medicine and Health Sciences Messenger RNA Nervous system Neurons Neuropeptides Physiological aspects Planarians - genetics Planarians - growth & development Platyhelminthes Pluripotent Stem Cells Regeneration - genetics RNA Interference RNA, Messenger - genetics Stem cell research Stem cells Studies Transcription factors |
title | COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians |
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