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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Veröffentlicht in:PLoS genetics 2014-10, Vol.10 (10), p.e1004746-e1004746
Hauptverfasser: Cowles, Martis W, Omuro, Kerilyn C, Stanley, Brianna N, Quintanilla, Carlo G, Zayas, Ricardo M
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Omuro, Kerilyn C
Stanley, Brianna N
Quintanilla, Carlo G
Zayas, Ricardo M
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</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. 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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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