Title: Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system
Authors: Weng, Qinjie ×
Chen, Ying
Wang, Haibo
Xu, Xiaomei
Yang, Bo
Shou, Weinian
Chen, Yangyin
Higashi, Yujiro
van den Berghe, Veronique
Seuntjens, Eve
Kernie, Steven G
Bukshpun, Polina
Sherr, Elliott H
Huylebroeck, Danny #
Issue Date: Feb-2012
Publisher: Cell Press
Series Title: Neuron vol:73 issue:4 pages:713-728
Abstract: Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair.
ISSN: 0896-6273
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Embryo and Stemcells (-)
× corresponding author
# (joint) last author

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