PUBLICATION

Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway

Authors
Chang, J.T., Lehtinen, M.K., Sive, H.
ID
ZDB-PUB-150520-16
Date
2016
Source
Developmental Neurobiology   76(1): 75-92 (Journal)
Registered Authors
Chang, Jessica, Sive, Hazel
Keywords
RBP4, brain development, cell survival, cerebrospinal fluid, retinoic acid
MeSH Terms
  • Retinoids/metabolism*
  • Cell Death
  • Animals
  • Cell Survival
  • Zebrafish/metabolism*
  • Cerebral Ventricles/metabolism
  • Retinol-Binding Proteins, Plasma/metabolism*
  • Zebrafish Proteins/metabolism*
  • Tretinoin/cerebrospinal fluid
  • Signal Transduction/physiology*
(all 10)
PubMed
25980532 Full text @ Dev. Neurobiol.
Abstract
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. This article is protected by copyright. All rights reserved.
Genes / Markers
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nl1TgTransgenic Insertion
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    Sequence Targeting Reagents
    Target Reagent Reagent Type
    rbp4MO2-rbp4MRPHLNO
    tp53MO4-tp53MRPHLNO
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    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
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