期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 25, 页码 9697-9702出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0603373103
关键词
neural progenitor cell; neural stem cell; neurogenesis
资金
- NIA NIH HHS [AG 19193, R01 AG019193] Funding Source: Medline
- NICHD NIH HHS [P30 HD 02274, P30 HD002274] Funding Source: Medline
- NIDDK NIH HHS [P30 DK056465, DK 56465] Funding Source: Medline
- NIGMS NIH HHS [T32 GM 07750, T32 GM007750] Funding Source: Medline
Multipotent cortical progenitor cells differentiate into neurons and glial cells during development; however, mechanisms governing the specification of progenitors to a neuronal fate are not well understood. Although both extrinsic and intrinsic factors regulate this process, little is known about kinase signaling mechanisms that direct neuronal fate. Here, we report that extracellular signal-regulated kinase (ERK)5 is expressed and active in proliferating cortical progenitors. Lentiviral gene delivery of a dominant negative ERK5 or dominant negative MAP kinase kinase 5 reduced the number of neurons generated from rat cortical progenitor cells in culture, whereas constitutive activation of ERK5 increased the production of neurons. Furthermore, when cortical progenitor cells were treated with ciliary neurotrophic factor, which induces precocious glial differentiation, ERK5 activation still promoted neuronal fate while suppressing glial differentiation. Our data also indicate that ERK5 does not directly regulate proliferation or apoptosis of cultured cortical progenitors. We conclude that ERKS is necessary and sufficient to stimulate the generation of neurons from cortical progenitors. These results suggest a previously uncharacterized function for ERK5 signaling during brain development and raise the interesting possibility that extrinsic factors may instruct cortical progenitors to become neurons by activating the ERK5 pathway.
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