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Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish

BACKGROUND: Regulated secretion of specialized neuropeptides in the vertebrate neuroendocrine system is critical for ensuring physiological homeostasis. Expression of these cell-specific peptide markers in the differentiating hypothalamus commences prior to birth, often predating the physiological d...

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Autores principales: Kurrasch, Deborah M, Nevin, Linda M, Wong, Jinny S, Baier, Herwig, Ingraham, Holly A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715394/
https://www.ncbi.nlm.nih.gov/pubmed/19549326
http://dx.doi.org/10.1186/1749-8104-4-22
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author Kurrasch, Deborah M
Nevin, Linda M
Wong, Jinny S
Baier, Herwig
Ingraham, Holly A
author_facet Kurrasch, Deborah M
Nevin, Linda M
Wong, Jinny S
Baier, Herwig
Ingraham, Holly A
author_sort Kurrasch, Deborah M
collection PubMed
description BACKGROUND: Regulated secretion of specialized neuropeptides in the vertebrate neuroendocrine system is critical for ensuring physiological homeostasis. Expression of these cell-specific peptide markers in the differentiating hypothalamus commences prior to birth, often predating the physiological demand for secreted neuropeptides. The conserved function and spatial expression of hypothalamic peptides in vertebrates prompted us to search for critical neuroendocrine genes in newly hatched zebrafish larvae. RESULTS: We screened mutant 5 days post-fertilization zebrafish larvae that fail to undergo visually mediated background adaptation for disruption in hypothalamic pomc expression. To our surprise, the ATPase N-ethylmaleimide sensitive factor (nsf) was identified as an essential gene for maintenance of neuroendocrine transcriptional programs during the embryo-to-larva transition. Despite normal hypothalamic development in nsf(st53 )mutants, neuropeptidergic cells exhibited a dramatic loss of cell-specific markers by 5 days post-fertilization that is accompanied by elevated intracellular neuropeptide protein. Consistent with the role of NSF in vesicle-membrane fusion events and intracellular trafficking, cytoplasmic endoplasmic reticulum-like membranes accumulate in nsf(-/- )hypothalamic neurons similar to that observed for SEC18 (nsf ortholog) yeast mutants. Our data support a model in which unspent neuropeptide cargo feedbacks to extinguish transcription in neuropeptidergic cells just as they become functionally required. In support of this model we found that gnrh3 transcripts remained unchanged in pre-migratory, non-functional gonadotropin-releasing hormone (GnRH) neurons in nsf(-/- )zebrafish. Furthermore, oxytocin-like (oxtl, intp) transcripts, which are found in osmoreceptive neurons and persist in mutant zebrafish, drop precipitously after mutant zebrafish are acutely challenged with high salt. CONCLUSION: Our analyses of nsf mutant zebrafish reveal an unexpected role for NSF in hypothalamic development, with mutant 5 days post-fertilization larvae exhibiting a stage-dependent loss of neuroendocrine transcripts and a corresponding accumulation of neuropeptides in the soma. Based on our collective findings, we speculate that neuroendocrine transcriptional programs adapt dynamically to both the supply and demand for neuropeptides to ensure adequate homeostatic responses.
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spelling pubmed-27153942009-07-25 Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish Kurrasch, Deborah M Nevin, Linda M Wong, Jinny S Baier, Herwig Ingraham, Holly A Neural Dev Research Article BACKGROUND: Regulated secretion of specialized neuropeptides in the vertebrate neuroendocrine system is critical for ensuring physiological homeostasis. Expression of these cell-specific peptide markers in the differentiating hypothalamus commences prior to birth, often predating the physiological demand for secreted neuropeptides. The conserved function and spatial expression of hypothalamic peptides in vertebrates prompted us to search for critical neuroendocrine genes in newly hatched zebrafish larvae. RESULTS: We screened mutant 5 days post-fertilization zebrafish larvae that fail to undergo visually mediated background adaptation for disruption in hypothalamic pomc expression. To our surprise, the ATPase N-ethylmaleimide sensitive factor (nsf) was identified as an essential gene for maintenance of neuroendocrine transcriptional programs during the embryo-to-larva transition. Despite normal hypothalamic development in nsf(st53 )mutants, neuropeptidergic cells exhibited a dramatic loss of cell-specific markers by 5 days post-fertilization that is accompanied by elevated intracellular neuropeptide protein. Consistent with the role of NSF in vesicle-membrane fusion events and intracellular trafficking, cytoplasmic endoplasmic reticulum-like membranes accumulate in nsf(-/- )hypothalamic neurons similar to that observed for SEC18 (nsf ortholog) yeast mutants. Our data support a model in which unspent neuropeptide cargo feedbacks to extinguish transcription in neuropeptidergic cells just as they become functionally required. In support of this model we found that gnrh3 transcripts remained unchanged in pre-migratory, non-functional gonadotropin-releasing hormone (GnRH) neurons in nsf(-/- )zebrafish. Furthermore, oxytocin-like (oxtl, intp) transcripts, which are found in osmoreceptive neurons and persist in mutant zebrafish, drop precipitously after mutant zebrafish are acutely challenged with high salt. CONCLUSION: Our analyses of nsf mutant zebrafish reveal an unexpected role for NSF in hypothalamic development, with mutant 5 days post-fertilization larvae exhibiting a stage-dependent loss of neuroendocrine transcripts and a corresponding accumulation of neuropeptides in the soma. Based on our collective findings, we speculate that neuroendocrine transcriptional programs adapt dynamically to both the supply and demand for neuropeptides to ensure adequate homeostatic responses. BioMed Central 2009-06-23 /pmc/articles/PMC2715394/ /pubmed/19549326 http://dx.doi.org/10.1186/1749-8104-4-22 Text en Copyright © 2009 Kurrasch et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kurrasch, Deborah M
Nevin, Linda M
Wong, Jinny S
Baier, Herwig
Ingraham, Holly A
Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish
title Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish
title_full Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish
title_fullStr Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish
title_full_unstemmed Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish
title_short Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish
title_sort neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in nsf mutant zebrafish
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715394/
https://www.ncbi.nlm.nih.gov/pubmed/19549326
http://dx.doi.org/10.1186/1749-8104-4-22
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