GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation
Summary: Neurons and oligodendrocytes communicate to regulate oligodendrocyte development and ensure appropriate axonal myelination. Here, we show that Glycerophosphodiester phosphodiesterase 2 (GDE2) signaling underlies a neuronal pathway that promotes oligodendrocyte maturation through the release...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472030440X |
| _version_ | 1818276120404951040 |
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| author | Bo-Ran Choi Clinton Cave Chan Hyun Na Shanthini Sockanathan |
| author_facet | Bo-Ran Choi Clinton Cave Chan Hyun Na Shanthini Sockanathan |
| author_sort | Bo-Ran Choi |
| collection | DOAJ |
| description | Summary: Neurons and oligodendrocytes communicate to regulate oligodendrocyte development and ensure appropriate axonal myelination. Here, we show that Glycerophosphodiester phosphodiesterase 2 (GDE2) signaling underlies a neuronal pathway that promotes oligodendrocyte maturation through the release of soluble neuronally derived factors. Mice lacking global or neuronal GDE2 expression have reduced mature oligodendrocytes and myelin proteins but retain normal numbers of oligodendrocyte precursor cells (OPCs). Wild-type (WT) OPCs cultured in conditioned medium (CM) from Gde2-null (Gde2KO) neurons exhibit delayed maturation, recapitulating in vivo phenotypes. Gde2KO neurons show robust reduction in canonical Wnt signaling, and genetic activation of Wnt signaling in Gde2KO neurons rescues in vivo and in vitro oligodendrocyte maturation. Phosphacan, a known stimulant of oligodendrocyte maturation, is reduced in CM from Gde2KO neurons but is restored when Wnt signaling is activated. These studies identify GDE2 control of Wnt signaling as a neuronal pathway that signals to oligodendroglia to promote oligodendrocyte maturation. |
| first_indexed | 2024-12-12T22:40:36Z |
| format | Article |
| id | doaj.art-4c21fc934f6848cf9db2fd96e3d59ac0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T22:40:36Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4c21fc934f6848cf9db2fd96e3d59ac02022-12-22T00:09:19ZengElsevierCell Reports2211-12472020-05-01315GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte MaturationBo-Ran Choi0Clinton Cave1Chan Hyun Na2Shanthini Sockanathan3The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, PCTB 1004, Baltimore, MD 21205, USANeuroscience Program, Middlebury College, 276 Bicentennial Way, MBH 351, Middlebury, VT 05753, USADepartment of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, MRB 753, Baltimore, MD 21205, USAThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, PCTB 1004, Baltimore, MD 21205, USA; Corresponding authorSummary: Neurons and oligodendrocytes communicate to regulate oligodendrocyte development and ensure appropriate axonal myelination. Here, we show that Glycerophosphodiester phosphodiesterase 2 (GDE2) signaling underlies a neuronal pathway that promotes oligodendrocyte maturation through the release of soluble neuronally derived factors. Mice lacking global or neuronal GDE2 expression have reduced mature oligodendrocytes and myelin proteins but retain normal numbers of oligodendrocyte precursor cells (OPCs). Wild-type (WT) OPCs cultured in conditioned medium (CM) from Gde2-null (Gde2KO) neurons exhibit delayed maturation, recapitulating in vivo phenotypes. Gde2KO neurons show robust reduction in canonical Wnt signaling, and genetic activation of Wnt signaling in Gde2KO neurons rescues in vivo and in vitro oligodendrocyte maturation. Phosphacan, a known stimulant of oligodendrocyte maturation, is reduced in CM from Gde2KO neurons but is restored when Wnt signaling is activated. These studies identify GDE2 control of Wnt signaling as a neuronal pathway that signals to oligodendroglia to promote oligodendrocyte maturation.http://www.sciencedirect.com/science/article/pii/S221112472030440XGDE2oligodendrocyte maturationmyelinationWnt signalingphosphacan |
| spellingShingle | Bo-Ran Choi Clinton Cave Chan Hyun Na Shanthini Sockanathan GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation Cell Reports GDE2 oligodendrocyte maturation myelination Wnt signaling phosphacan |
| title | GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation |
| title_full | GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation |
| title_fullStr | GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation |
| title_full_unstemmed | GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation |
| title_short | GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation |
| title_sort | gde2 dependent activation of canonical wnt signaling in neurons regulates oligodendrocyte maturation |
| topic | GDE2 oligodendrocyte maturation myelination Wnt signaling phosphacan |
| url | http://www.sciencedirect.com/science/article/pii/S221112472030440X |
| work_keys_str_mv | AT boranchoi gde2dependentactivationofcanonicalwntsignalinginneuronsregulatesoligodendrocytematuration AT clintoncave gde2dependentactivationofcanonicalwntsignalinginneuronsregulatesoligodendrocytematuration AT chanhyunna gde2dependentactivationofcanonicalwntsignalinginneuronsregulatesoligodendrocytematuration AT shanthinisockanathan gde2dependentactivationofcanonicalwntsignalinginneuronsregulatesoligodendrocytematuration |