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Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain

In rodents, the Npas4 gene has recently been identified as being an important regulator of synaptic plasticity and memory. Homologs of Npas4 have been found in invertebrate species though their functions appear to be too divergent for them to be studied as a proxy for the mammalian proteins. The aim...

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Autores principales: Klarić, Thomas, Lardelli, Michael, Key, Brian, Koblar, Simon, Lewis, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255624/
https://www.ncbi.nlm.nih.gov/pubmed/25538572
http://dx.doi.org/10.3389/fnana.2014.00148
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author Klarić, Thomas
Lardelli, Michael
Key, Brian
Koblar, Simon
Lewis, Martin
author_facet Klarić, Thomas
Lardelli, Michael
Key, Brian
Koblar, Simon
Lewis, Martin
author_sort Klarić, Thomas
collection PubMed
description In rodents, the Npas4 gene has recently been identified as being an important regulator of synaptic plasticity and memory. Homologs of Npas4 have been found in invertebrate species though their functions appear to be too divergent for them to be studied as a proxy for the mammalian proteins. The aim of this study, therefore, was to ascertain the suitability of the zebrafish as a model organism for investigating the function of Npas4 genes. We show here that the expression and regulation of the zebrafish Npas4 homolog, npas4a, is remarkably similar to that of the rodent Npas4 genes. As in mammals, expression of the zebrafish npas4a gene is restricted to the brain where it is up-regulated in response to neuronal activity. Furthermore, we also show that knockdown of npas4a during embryonic development results in a number of forebrain-specific defects including increased apoptosis and misexpression of the forebrain marker genes dlx1a and shha. Our work demonstrates that the zebrafish is a suitable model organism for investigating the role of the npas4a gene and one that is likely to provide valuable insights into the function of the mammalian homologs. Furthermore, our findings highlight a potential role for npas4a in forebrain development.
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spelling pubmed-42556242014-12-23 Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain Klarić, Thomas Lardelli, Michael Key, Brian Koblar, Simon Lewis, Martin Front Neuroanat Neuroscience In rodents, the Npas4 gene has recently been identified as being an important regulator of synaptic plasticity and memory. Homologs of Npas4 have been found in invertebrate species though their functions appear to be too divergent for them to be studied as a proxy for the mammalian proteins. The aim of this study, therefore, was to ascertain the suitability of the zebrafish as a model organism for investigating the function of Npas4 genes. We show here that the expression and regulation of the zebrafish Npas4 homolog, npas4a, is remarkably similar to that of the rodent Npas4 genes. As in mammals, expression of the zebrafish npas4a gene is restricted to the brain where it is up-regulated in response to neuronal activity. Furthermore, we also show that knockdown of npas4a during embryonic development results in a number of forebrain-specific defects including increased apoptosis and misexpression of the forebrain marker genes dlx1a and shha. Our work demonstrates that the zebrafish is a suitable model organism for investigating the role of the npas4a gene and one that is likely to provide valuable insights into the function of the mammalian homologs. Furthermore, our findings highlight a potential role for npas4a in forebrain development. Frontiers Media S.A. 2014-12-04 /pmc/articles/PMC4255624/ /pubmed/25538572 http://dx.doi.org/10.3389/fnana.2014.00148 Text en Copyright © 2014 Klarić, Lardelli, Key, Koblar and Lewis. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Klarić, Thomas
Lardelli, Michael
Key, Brian
Koblar, Simon
Lewis, Martin
Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain
title Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain
title_full Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain
title_fullStr Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain
title_full_unstemmed Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain
title_short Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain
title_sort activity-dependent expression of neuronal pas domain-containing protein 4 (npas4a) in the developing zebrafish brain
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255624/
https://www.ncbi.nlm.nih.gov/pubmed/25538572
http://dx.doi.org/10.3389/fnana.2014.00148
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