Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
| Autor: | Amir Al Oustah, Cathy Danesin, Philippe Cochard, Nathalie Escalas, David Ohayon, Bruno Glise, Cathy Soula, Vanessa Bouguetoch, Romain Darche-Gabinaud |
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| Přispěvatelé: | Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell type animal structures Interneuron Neurogenesis Science [SDV]Life Sciences [q-bio] Stem cells Biology Article OLIG2 03 medical and health sciences 0302 clinical medicine SULF1 Interneurons Developmental biology medicine Animals Hedgehog Proteins Progenitor cell Sonic hedgehog Extracellular sulfatase Zebrafish 030304 developmental biology Oligodendrocyte Precursor Cells 0303 health sciences Multidisciplinary Gene Expression Regulation Developmental Zebrafish Proteins biology.organism_classification Cell biology Oligodendroglia 030104 developmental biology medicine.anatomical_structure Sulfatase 2 Spinal Cord embryonic structures biology.protein Gliogenesis Medicine Heparitin Sulfate Sulfatases 030217 neurology & neurosurgery Morphogen Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2021, 11 (1), ⟨10.1038/s41598-020-80455-2⟩ Scientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-80455-2⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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