PUBLICATION

Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain

Authors
Sosnik, J., Zheng, L., Rackauckas, C.V., Digman, M., Gratton, E., Nie, Q., Schilling, T.F.
ID
ZDB-PUB-160414-14
Date
2016
Source
eLIFE   5: e14034 (Journal)
Registered Authors
Schilling, Tom, Sosnik, Julian
Keywords
Danio rerio, computational biology, developmental biology, hindbrain, morphogen, noise, retinoic acid, rhombomere, stem cells, systems biology, zebrafish
MeSH Terms
  • Signal Transduction*
  • Rhombencephalon/embryology*
  • Tretinoin/metabolism*
  • Zebrafish/embryology*
  • Gene Expression Regulation, Developmental*
  • Animals
(all 6)
PubMed
27067377 Full text @ Elife
Abstract
Morphogen gradients induce sharply defined domains of gene expression in a concentration-dependent manner, yet how cells interpret these signals in the face of spatial and temporal noise remains unclear. Using fluorescence lifetime imaging microscopy (FLIM) and phasor analysis to measure endogenous retinoic acid (RA) directly in vivo, we have investigated the amplitude of noise in RA signaling, and how modulation of this noise affects patterning of hindbrain segments (rhombomeres) in the zebrafish embryo. We demonstrate that RA forms a noisy gradient during critical stages of hindbrain patterning and that cells use distinct intracellular binding proteins to attenuate noise in RA levels. Increasing noise disrupts sharpening of rhombomere boundaries and proper patterning of the hindbrain. These findings reveal novel cellular mechanisms of noise regulation, which are likely to play important roles in other aspects of physiology and disease.
Genes / Markers
Marker Marker Type Name
aldh1a2GENEaldehyde dehydrogenase 1 family, member A2
crabp2aGENEcellular retinoic acid binding protein 2, a
cyp26a1GENEcytochrome P450, family 26, subfamily A, polypeptide 1
egr2bGENEearly growth response 2b
hoxb1aGENEhomeobox B1a
1 - 5 of 5
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Figures
Figure Gallery (4 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf278EtTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    aldh1a2MO1-aldh1a2MRPHLNO
    crabp2aMO1-crabp2aMRPHLNO
    crabp2aMO2-crabp2aMRPHLNO
    cyp26a1MO1-cyp26a1MRPHLNO
    1 - 4 of 4
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    Fish
    No data available
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    KALTA4EFGKALTA4
    mCherryEFGmCherry
    1 - 2 of 2
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    Mapping
    No data available
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    Citation
    Sosnik, J., Zheng, L., Rackauckas, C.V., Digman, M., Gratton, E., Nie, Q., Schilling, T.F. (2016) Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain. eLIFE. 5:e14034.