PUBLICATION

Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord

Authors
Danesin, C., Darche-Gabinaud, R., Escalas, N., Bouguetoch, V., Cochard, P., Al Oustah, A., Ohayon, D., Glise, B., Soula, C.
ID
ZDB-PUB-210110-5
Date
2021
Source
Scientific Reports   11: 118 (Journal)
Registered Authors
Al Oustah, Amir, Danesin, Cathy, Glise, Bruno, Soula, Cathy
Keywords
none
MeSH Terms
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism*
  • Sulfatases/genetics
  • Sulfatases/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Oligodendrocyte Precursor Cells/metabolism
  • Animals
  • Heparitin Sulfate/metabolism
  • Spinal Cord/growth & development*
  • Spinal Cord/metabolism
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Interneurons/metabolism
  • Gene Expression Regulation, Developmental
  • Oligodendroglia/metabolism
(all 18)
PubMed
33420239 Full text @ Sci. Rep.
Abstract
Sulf2a belongs to the Sulf family of extracellular sulfatases which selectively remove 6-O-sulfate groups from heparan sulfates, a critical regulation level for their role in modulating the activity of signalling molecules. Data presented here define Sulf2a as a novel player in the control of Sonic Hedgehog (Shh)-mediated cell type specification during spinal cord development. We show that Sulf2a depletion in zebrafish results in overproduction of V3 interneurons at the expense of motor neurons and also impedes generation of oligodendrocyte precursor cells (OPCs), three cell types that depend on Shh for their generation. We provide evidence that Sulf2a, expressed in a spatially restricted progenitor domain, acts by maintaining the correct patterning and specification of ventral progenitors. More specifically, Sulf2a prevents Olig2 progenitors to activate high-threshold Shh response and, thereby, to adopt a V3 interneuron fate, thus ensuring proper production of motor neurons and OPCs. We propose a model in which Sulf2a reduces Shh signalling levels in responding cells by decreasing their sensitivity to the morphogen factor. More generally, our work, revealing that, in contrast to its paralog Sulf1, Sulf2a regulates neural fate specification in Shh target cells, provides direct evidence of non-redundant functions of Sulfs in the developing spinal cord.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
umz23TgTransgenic Insertion
    ups9
      Indel
      vu12TgTransgenic Insertion
        vu17TgTransgenic Insertion
          vu19TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            sulf2aCRISPR1-sulf2aCRISPR
            sulf2aMO1-sulf2aMRPHLNO
            sulf2aMO3-sulf2aMRPHLNO
            1 - 3 of 3
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            Fish
            Antibodies
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRed2EFGDsRed2
            EGFPEFGEGFP
            1 - 2 of 2
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            Mapping
            No data available