期刊
GLIA
卷 60, 期 6, 页码 851-866出版社
WILEY
DOI: 10.1002/glia.22316
关键词
optic nerve; Ptc-1; Gli1; internalization; astrocyte; LRP2
资金
- Fondo de Investigaciones Sanitarias (FIS) [RD07-0060]
- ISCIII [ADE10/0010]
- Gobierno de Castilla La Mancha [PI2010-012, PI2009/26, MOV2007-JI/20]
- Fundacion Eugenio Rodriguez Pascual
- NICHD
- Ministerio de Ciencia e Innovacion (MICINN) [SAF2009-07845]
- SESCAM
Oligodendrocyte precursor cells (OPCs) of the optic nerve are generated in the preoptic area, from where they migrate to colonize it entirely. Sonic hedgehog (Shh) induces the proliferation of these cells as well as influencing their migration, acting through its canonical receptor (Ptc-1). However, the multiligand receptor megalin (or LRP-2) is also involved in Shh-induced OPC proliferation and migration, and thus, we have evaluated the relevance of this interaction. During the stages at which Shh influences OPC development, we found megalin to be selectively expressed by optic nerve astrocytes, whereas Ptc-1 and Gli1 were found in OPCs. Indeed, this pattern of expression paralleled the rostralcaudal expression of the three Shh-related molecules during the time course of plp-dm20+-OPC colonization. The blockage of megalin partially abolished OPC chemoattraction and fully impaired Shh-induced proliferation. Using in vitro co-cultures of dissociated optic nerve cells, we demonstrated that Shh was internalized by astrocytes via megalin, and sufficient Shh was subsequently released to produce the biological effects on OPCs observed in the nerve. Together, these data indicate that at least part of the influence of Shh on OPCs is mediated by megalin during optic nerve development, and that astrocytes expressing megalin transiently capture Shh to present it to OPCs and/or to control the gradient of this molecule during development. (c) 2012 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据