Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system.
During neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subt...
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doaj-fcc6beb7e9834f7b9e649a7ca3fbbe632020-11-25T02:12:46ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0182e100250110.1371/journal.pgen.1002501Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system.Kevin T EadeHailey A FancherMarc S RidyardDouglas W AllanDuring neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and Tv4), we test whether the subtype transcription factor networks that direct differentiation during development are required persistently for long-term maintenance of subtype identity. By conditional transcription factor knockdown in adult Tv neurons after normal development, we find that most transcription factors within the Tv1/Tv4 subtype transcription networks are indeed required to maintain Tv1/Tv4 subtype-specific gene expression in adults. Thus, gene expression profiles are not simply "locked-in," but must be actively maintained by persistent developmental transcription factor networks. We also examined the cross-regulatory relationships between all transcription factors that persisted in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory relationships that had existed between these transcription factors during development were no longer present in the mature adult neuron. This points to key differences between developmental and maintenance transcriptional regulatory networks in individual neurons. Together, our results provide novel insight showing that the maintenance of subtype identity is an active process underpinned by persistently active, combinatorially-acting, developmental transcription factors. These findings have implications for understanding the maintenance of all long-lived cell types and the functional degeneration of neurons in the aging brain.http://europepmc.org/articles/PMC3285578?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kevin T Eade Hailey A Fancher Marc S Ridyard Douglas W Allan |
spellingShingle |
Kevin T Eade Hailey A Fancher Marc S Ridyard Douglas W Allan Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. PLoS Genetics |
author_facet |
Kevin T Eade Hailey A Fancher Marc S Ridyard Douglas W Allan |
author_sort |
Kevin T Eade |
title |
Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. |
title_short |
Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. |
title_full |
Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. |
title_fullStr |
Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. |
title_full_unstemmed |
Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. |
title_sort |
developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-01-01 |
description |
During neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and Tv4), we test whether the subtype transcription factor networks that direct differentiation during development are required persistently for long-term maintenance of subtype identity. By conditional transcription factor knockdown in adult Tv neurons after normal development, we find that most transcription factors within the Tv1/Tv4 subtype transcription networks are indeed required to maintain Tv1/Tv4 subtype-specific gene expression in adults. Thus, gene expression profiles are not simply "locked-in," but must be actively maintained by persistent developmental transcription factor networks. We also examined the cross-regulatory relationships between all transcription factors that persisted in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory relationships that had existed between these transcription factors during development were no longer present in the mature adult neuron. This points to key differences between developmental and maintenance transcriptional regulatory networks in individual neurons. Together, our results provide novel insight showing that the maintenance of subtype identity is an active process underpinned by persistently active, combinatorially-acting, developmental transcription factors. These findings have implications for understanding the maintenance of all long-lived cell types and the functional degeneration of neurons in the aging brain. |
url |
http://europepmc.org/articles/PMC3285578?pdf=render |
work_keys_str_mv |
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