Ablation of neuronal ADAM17 impairs oligodendrocyte differentiation and myelination.
Glia
; 68(6): 1148-1164, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-31851405
ABSTRACT
Myelin, one of the most important adaptations of vertebrates, is essential to ensure efficient propagation of the electric impulse in the nervous system and to maintain neuronal integrity. In the central nervous system (CNS), the development of oligodendrocytes and the process of myelination are regulated by the coordinated action of several positive and negative cell-extrinsic factors. We and others previously showed that secretases regulate the activity of proteins essential for myelination. We now report that the neuronal α-secretase ADAM17 controls oligodendrocyte differentiation and myelin formation in the CNS. Ablation of Adam17 in neurons impairs in vivo and in vitro oligodendrocyte differentiation, delays myelin formation throughout development and results in hypomyelination. Furthermore, we show that this developmental defect is, in part, the result of altered Notch/Jagged 1 signaling. Surprisingly, in vivo conditional loss of Adam17 in immature oligodendrocytes has no effect on myelin formation. Collectively, our data indicate that the neuronal α-secretase ADAM17 is required for proper CNS myelination. Further, our studies confirm that secretases are important post-translational regulators of myelination although the mechanisms controlling CNS and peripheral nervous system (PNS) myelination are distinct.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sistema Nervioso Central
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Oligodendroglía
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Proteína ADAM17
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Vaina de Mielina
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Glia
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia