Wnt/β-catenin signaling in midbrain dopaminergic neuron specification and neurogenesis

作     者：Milan Joksimovic Rajeshwar Awatramani 

作者机构：Department of Cell Biology Neurobiology and Anatomy Medical College of Wisconsin 8701_ Watertown Plank Road Milwaukee Wl 53226-0509 USA Department of Neurology and Center for Genetic Medicine Northwestern University 303 E Superior Street Chicago IL 6061.1 USA 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2014年第8卷第1期

页      面：27-33页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 08[工学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：supported by the Whitehall Foundation Parkinson's Disease Foundation Brain Research Foundation 

主　　题：wnt β-catenin dopamine specification neurogenesis 

摘      要：Loss of midbrain dopaminergic （mDA） neurons underlies the motor symptoms of Parkinson＇s 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 [3-catenin, an obligate component of the Wnt cascade that is critical to mDA specification and neuro- genesis, mDA neurons have a unique origin--the midbrain fLoor plate （FP）. Unlike the hindbrain and spinal cord FP, the midbrain FP is highly neurogenic and Wnt/β-catenin signaling is critical to this difference in neurogenic potential. In β-catenin loss-of-function experiments, the midbrain FP resembles the hindbrain FP, and key mDA progenitor genes such as Otx2, Lmxlo, MsxJ, 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 β-catenin *** experiments, the hindbrain FP expresses key mDA progenitor genes, and is highly neurogenic. Interestingly, when excessive β-catenin is supplied to the midbrain FP, less mDA neurons are produced sug- gesting that the dosage ofWntJ β-catenin signaling is critical. These studies of β-catenin have facilitated new protocols to derive mDA neurons from stem cells.