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COE Loss-of-Function Analysis Reveals a Genetic Program Underlying Maintenance and Regeneration of the Nervous System in Planarians
COE transcription factors are conserved across widely divergent animals and are crucial for organismal development. COE genes also play roles in adult animals and have been implicated in central nervous system (CNS) diseases; however, the function of COE in the post-embryonic CNS remains poorly understood. Planarian regeneration provides an excellent model to study the function of transcription factors in cell differentiation and in terminally differentiated cells. In planarians, coe is expressed in differentiating and mature neurons, and its function is required for CNS regeneration. In this study, we show that coe is required to maintain structure and function of the CNS in uninjured planarians. We took advantage of this phenotype to identify genes regulated by coe by comparing global gene expression changes between control and coe mRNA-deficient planarians. This approach revealed downregulated genes downstream of coe with biological roles in CNS function. Expression analysis of downregulated genes uncovered previously unknown candidate targets of coe in the CNS. Furthermore, functional analysis of downstream targets identified coe-regulated genes required for CNS regeneration. These results demonstrate that the roles of COE in stem cell specification and neuronal function are active and indispensable during CNS renewal in adult animals.
Vyšlo v časopise: COE Loss-of-Function Analysis Reveals a Genetic Program Underlying Maintenance and Regeneration of the Nervous System in Planarians. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004746
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004746Souhrn
COE transcription factors are conserved across widely divergent animals and are crucial for organismal development. COE genes also play roles in adult animals and have been implicated in central nervous system (CNS) diseases; however, the function of COE in the post-embryonic CNS remains poorly understood. Planarian regeneration provides an excellent model to study the function of transcription factors in cell differentiation and in terminally differentiated cells. In planarians, coe is expressed in differentiating and mature neurons, and its function is required for CNS regeneration. In this study, we show that coe is required to maintain structure and function of the CNS in uninjured planarians. We took advantage of this phenotype to identify genes regulated by coe by comparing global gene expression changes between control and coe mRNA-deficient planarians. This approach revealed downregulated genes downstream of coe with biological roles in CNS function. Expression analysis of downregulated genes uncovered previously unknown candidate targets of coe in the CNS. Furthermore, functional analysis of downstream targets identified coe-regulated genes required for CNS regeneration. These results demonstrate that the roles of COE in stem cell specification and neuronal function are active and indispensable during CNS renewal in adult animals.
Zdroje
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