RT Journal Article
T1 TACE/ADAM17 Is Essential for Oligodendrocyte Development and CNS Myelination
A1 Palazuelos Diego, Javier
A1 Crawford, Howard
A1 Klingener, Michael
A1 Sun, Bingru
A1 Karelis, Jason
A1 Raines, Elaine
A1 Aguirre, Adan
AB Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination.
PB Society for Neuroscience
SN 0270-6474
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/91020
UL https://hdl.handle.net/20.500.14352/91020
LA eng
NO Palazuelos, Javier, et al. «TACE/ADAM17 Is Essential for Oligodendrocyte Development and CNS Myelination». The Journal of Neuroscience, vol. 34, n.o 36, septiembre de 2014, pp. 11884-96. https://doi.org/10.1523/JNEUROSCI.1220-14.2014.
NO National Institutes of Health
NO National Multiple Sclerosis Society
DS Docta Complutense
RD 17 abr 2025