Andersson E, Jensen J B, Parmar M, Guillemot F, Björklund A
Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, Sweden.
Development. 2006 Feb;133(3):507-16. doi: 10.1242/dev.02224. Epub 2006 Jan 5.
Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of the normal mesDA neuron number remain in Ngn2 mutant mice at postnatal stages. Analysis of Ngn2 mutant mice during mesDA neurogenesis show that medially located precursors are formed but are arrested in their differentiation at a stage when they have not yet acquired the characteristics of mesDA neuron precursors. Loss of Ngn2 function appears to specifically affect the generation of DA neurons, as the development of other types of neurons within the ventral midbrain is unaltered. Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain.
神经生成素2（Ngn2）是一种原神经基因，参与神经系统各区域的神经元分化和亚型特化。在腹侧中脑，Ngn2以一种时空模式表达，这种模式与中脑多巴胺能（mesDA）神经元的产生相关。我们在此表明，Ngn2的缺失会损害mesDA神经元的发育，以至于在出生后阶段，Ngn2突变小鼠中留存的mesDA神经元数量不到正常数量的一半。对mesDA神经发生过程中的Ngn2突变小鼠进行分析表明，位于内侧的前体细胞能够形成，但在尚未获得mesDA神经元前体细胞特征的阶段就停止了分化。Ngn2功能的丧失似乎特异性地影响了多巴胺能神经元的产生，因为腹侧中脑内其他类型神经元的发育并未改变。Ngn2是在mesDA神经元区域脑室区的祖细胞中表达的基因的首个例子，该基因对于mesDA神经元的正常分化至关重要，其功能丧失会导致mesDA神经发生受损，而腹侧中脑无其他主要异常。
