Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway

Cerebrospinal fluid (CSF) includes conserved factors whose function is largely unexplored. To assess the role of CSF during embryonic development, CSF was repeatedly drained from embryonic zebrafish brain ventricles soon after their inflation. Removal of CSF increased cell death in the diencephalon,...

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Main Authors: Lehtinen, Maria K., Chang, Jessica T., Sive, Hazel L.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Wiley Blackwell 2017
Online Access:http://hdl.handle.net/1721.1/108349
https://orcid.org/0000-0002-4890-424X
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author Lehtinen, Maria K.
Chang, Jessica T.
Sive, Hazel L.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Lehtinen, Maria K.
Chang, Jessica T.
Sive, Hazel L.
author_sort Lehtinen, Maria K.
collection MIT
description Cerebrospinal fluid (CSF) includes conserved factors whose function is largely unexplored. To assess the role of CSF during embryonic development, CSF was repeatedly drained from embryonic zebrafish brain ventricles soon after their inflation. Removal of CSF increased cell death in the diencephalon, indicating a survival function. Factors within the CSF are required for neuroepithelial cell survival as injected mouse CSF but not artificial CSF could prevent cell death after CSF depletion. Mass spectrometry analysis of the CSF identified retinol binding protein 4 (Rbp4), which transports retinol, the precursor to retinoic acid (RA). Consistent with a role for Rbp4 in cell survival, inhibition of Rbp4 or RA synthesis increased neuroepithelial cell death. Conversely, ventricle injection of exogenous human RBP4 plus retinol, or RA alone prevented cell death after CSF depletion. Zebrafish rbp4 is highly expressed in the yolk syncytial layer, suggesting Rbp4 protein and retinol/RA precursors can be transported into the CSF from the yolk. In accord with this suggestion, injection of human RBP4 protein into the yolk prevents neuroepithelial cell death in rbp4 loss-of-function embryos. Together, these data support the model that Rbp4 and RA precursors are present within the CSF and used for synthesis of RA, which promotes embryonic neuroepithelial survival.
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spelling mit-1721.1/1083492022-09-28T19:39:57Z Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway Lehtinen, Maria K. Chang, Jessica T. Sive, Hazel L. Massachusetts Institute of Technology. Department of Biology Chang, Jessica Tzung-Min Sive, Hazel L Cerebrospinal fluid (CSF) includes conserved factors whose function is largely unexplored. To assess the role of CSF during embryonic development, CSF was repeatedly drained from embryonic zebrafish brain ventricles soon after their inflation. Removal of CSF increased cell death in the diencephalon, indicating a survival function. Factors within the CSF are required for neuroepithelial cell survival as injected mouse CSF but not artificial CSF could prevent cell death after CSF depletion. Mass spectrometry analysis of the CSF identified retinol binding protein 4 (Rbp4), which transports retinol, the precursor to retinoic acid (RA). Consistent with a role for Rbp4 in cell survival, inhibition of Rbp4 or RA synthesis increased neuroepithelial cell death. Conversely, ventricle injection of exogenous human RBP4 plus retinol, or RA alone prevented cell death after CSF depletion. Zebrafish rbp4 is highly expressed in the yolk syncytial layer, suggesting Rbp4 protein and retinol/RA precursors can be transported into the CSF from the yolk. In accord with this suggestion, injection of human RBP4 protein into the yolk prevents neuroepithelial cell death in rbp4 loss-of-function embryos. Together, these data support the model that Rbp4 and RA precursors are present within the CSF and used for synthesis of RA, which promotes embryonic neuroepithelial survival. 2017-04-21T17:30:51Z 2017-04-21T17:30:51Z 2015-05 2015-05 Article http://purl.org/eprint/type/JournalArticle 1932-8451 1932-846X http://hdl.handle.net/1721.1/108349 Chang, Jessica T.; Lehtinen, Maria K. and Sive, Hazel. “Zebrafish Cerebrospinal Fluid Mediates Cell Survival through a Retinoid Signaling Pathway.” Developmental Neurobiology 76, no. 1 (June 8, 2015): 75–92. © 2015 The Authors https://orcid.org/0000-0002-4890-424X en_US http://dx.doi.org/10.1002/dneu.22300 Developmental Neurobiology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Wiley Blackwell Wiley
spellingShingle Lehtinen, Maria K.
Chang, Jessica T.
Sive, Hazel L.
Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
title Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
title_full Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
title_fullStr Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
title_full_unstemmed Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
title_short Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
title_sort zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
url http://hdl.handle.net/1721.1/108349
https://orcid.org/0000-0002-4890-424X
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