ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System
Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of p...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press
2020-06-01
|
| Series: | G3: Genes, Genomes, Genetics |
| Subjects: | |
| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.120.401126 |
| _version_ | 1819156564692434944 |
|---|---|
| author | Elyse L. Christensen Alexandra Beasley Jessica Radchuk Zachery E. Mielko Elicia Preston Sidney Stuckett John I. Murray Martin L. Hudson |
| author_facet | Elyse L. Christensen Alexandra Beasley Jessica Radchuk Zachery E. Mielko Elicia Preston Sidney Stuckett John I. Murray Martin L. Hudson |
| author_sort | Elyse L. Christensen |
| collection | DOAJ |
| description | Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis. |
| first_indexed | 2024-12-22T15:54:53Z |
| format | Article |
| id | doaj.art-bba0ee32e0614bccb220660a8e2d9db7 |
| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-22T15:54:53Z |
| publishDate | 2020-06-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-bba0ee32e0614bccb220660a8e2d9db72022-12-21T18:20:49ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362020-06-011061949196210.1534/g3.120.40112614ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous SystemElyse L. ChristensenAlexandra BeasleyJessica RadchukZachery E. MielkoElicia PrestonSidney StuckettJohn I. MurrayMartin L. HudsonProper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis.http://g3journal.org/lookup/doi/10.1534/g3.120.401126cell fate specificationbasic-helix-loop-helixrnaseqcomparative transcriptomeproneural |
| spellingShingle | Elyse L. Christensen Alexandra Beasley Jessica Radchuk Zachery E. Mielko Elicia Preston Sidney Stuckett John I. Murray Martin L. Hudson ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System G3: Genes, Genomes, Genetics cell fate specification basic-helix-loop-helix rnaseq comparative transcriptome proneural |
| title | ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System |
| title_full | ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System |
| title_fullStr | ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System |
| title_full_unstemmed | ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System |
| title_short | ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System |
| title_sort | ngn 1 neurogenin activates transcription of multiple terminal selector transcription factors in the caenorhabditis elegans nervous system |
| topic | cell fate specification basic-helix-loop-helix rnaseq comparative transcriptome proneural |
| url | http://g3journal.org/lookup/doi/10.1534/g3.120.401126 |
| work_keys_str_mv | AT elyselchristensen ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT alexandrabeasley ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT jessicaradchuk ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT zacheryemielko ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT eliciapreston ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT sidneystuckett ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT johnimurray ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem AT martinlhudson ngn1neurogeninactivatestranscriptionofmultipleterminalselectortranscriptionfactorsinthecaenorhabditiselegansnervoussystem |