期刊
JOURNAL OF MOLECULAR CELL BIOLOGY
卷 6, 期 1, 页码 27-33出版社
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjt043
关键词
wnt; -catenin; dopamine; specification; neurogenesis
类别
资金
- Whitehall Foundation
- Brain Research Foundation
- Parkinson's Disease Foundation
Loss of midbrain dopaminergic (mDA) neurons underlies the motor symptoms of Parkinsons disease. Towards cell replacement, studies have focused on mechanisms underlying embryonic mDA production, as a rational basis for deriving mDA neurons from stem cells. We will review studies of -catenin, an obligate component of the Wnt cascade that is critical to mDA specification and neurogenesis. mDA neurons have a unique originuthe midbrain floor plate (FP). Unlike the hindbrain and spinal cord FP, the midbrain FP is highly neurogenic and Wnt/-catenin signaling is critical to this difference in neurogenic potential. In -catenin loss-of-function experiments, the midbrain FP resembles the hindbrain FP, and key mDA progenitor genes such as Otx2, Lmx1a, Msx1, and Ngn2 are downregulated whereas Shh is maintained. Accordingly, the neurogenic capacity of the midbrain FP is diminished, resulting in fewer mDA neurons. Conversely, in -catenin gain-of-function experiments, the hindbrain FP expresses key mDA progenitor genes, and is highly neurogenic. Interestingly, when excessive -catenin is supplied to the midbrain FP, less mDA neurons are produced suggesting that the dosage of Wnt/-catenin signaling is critical. These studies of -catenin have facilitated new protocols to derive mDA neurons from stem cells.
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