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

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...

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Autores principales:	Cathy Danesin, Romain Darche-Gabinaud, Nathalie Escalas, Vanessa Bouguetoch, Philippe Cochard, Amir Al Oustah, David Ohayon, Bruno Glise, Cathy Soula
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29c28ef9ccb14568b3b9318f840c8eca
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spelling	oai:doaj.org-article:29c28ef9ccb14568b3b9318f840c8eca2021-12-02T15:08:23ZSulf2a controls Shh-dependent neural fate specification in the developing spinal cord10.1038/s41598-020-80455-22045-2322https://doaj.org/article/29c28ef9ccb14568b3b9318f840c8eca2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80455-2https://doaj.org/toc/2045-2322Abstract 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.Cathy DanesinRomain Darche-GabinaudNathalie EscalasVanessa BouguetochPhilippe CochardAmir Al OustahDavid OhayonBruno GliseCathy SoulaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cathy Danesin Romain Darche-Gabinaud Nathalie Escalas Vanessa Bouguetoch Philippe Cochard Amir Al Oustah David Ohayon Bruno Glise Cathy Soula Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
description	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.
format	article
author	Cathy Danesin Romain Darche-Gabinaud Nathalie Escalas Vanessa Bouguetoch Philippe Cochard Amir Al Oustah David Ohayon Bruno Glise Cathy Soula
author_facet	Cathy Danesin Romain Darche-Gabinaud Nathalie Escalas Vanessa Bouguetoch Philippe Cochard Amir Al Oustah David Ohayon Bruno Glise Cathy Soula
author_sort	Cathy Danesin
title	Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
title_short	Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
title_full	Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
title_fullStr	Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
title_full_unstemmed	Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
title_sort	sulf2a controls shh-dependent neural fate specification in the developing spinal cord
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29c28ef9ccb14568b3b9318f840c8eca
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Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord

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