Calcineurin/NFAT Signaling Is Required for Neuregulin-Regulated Schwann Cell Differentiation

被引：173

作者：

Kao, Shih-Chu ^{[1
,2
,3
]}

Wu, Hai ^{[1
,2
,3
]}

Xie, Jianming ^{[3
]}

Chang, Ching-Pin ^{[1
,2
,3
]}

Ranish, Jeffrey A. ^{[4
]}

Graef, Isabella A. ^{[1
,2
]}

Crabtree, Gerald R. ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA

[3] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

[4] Inst Syst Biol, Seattle, WA 98103 USA

来源：

SCIENCE | 2009年 / 323卷 / 5914期

关键词：

TRANSCRIPTION FACTOR SOX10; PERIPHERAL NERVOUS-SYSTEM; HEART DEVELOPMENT; AXONAL REGULATION; NUCLEAR FACTOR; MYELINATION; SURVIVAL; PROLIFERATION; NERVES; OCT-6;

D O I：

10.1126/science.1166562

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking calcineurin B1 in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate Krox20, which regulates genes necessary for myelination. Our studies demonstrate that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural crest diversification, and differentiation of Schwann cells.

引用

页码：651 / 654

页数：4

共 29 条

[1] NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21 [J].