Storm Robert, Cholewa-Waclaw Justyna, Reuter Katja, Bröhl Dominique, Sieber Martin, Treier Mathias, Müller Thomas, Birchmeier Carmen
Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Development. 2009 Jan;136(2):295-305. doi: 10.1242/dev.027193. Epub 2008 Dec 15.
The Olig3 gene encodes a bHLH factor that is expressed in the ventricular zone of the dorsal alar plate of the hindbrain. We found that the Olig3(+) progenitor domain encompassed subdomains that co-expressed Math1, Ngn1, Mash1 and Ptf1a. Olig3(+) cells give rise to neuronal types in the dorsal alar plate that we denote as class A neurons. We used genetic lineage tracing to demonstrate that class A neurons contribute to the nucleus of the solitary tract and to precerebellar nuclei. The fate of class A neurons was not correctly determined in Olig3 mutant mice. As a consequence, the nucleus of the solitary tract did not form, and precerebellar nuclei, such as the inferior olivary nucleus, were absent or small. At the expense of class A neurons, ectopic Lbx1(+) neurons appeared in the alar plate in Olig3 mutant mice. By contrast, electroporation of an Olig3 expression vector in the chick hindbrain suppressed the emergence of Lbx1(+) neurons. Climbing fiber neurons of the inferior olivary nucleus express Foxd3 and require Olig3 as well as Ptf1a for the determination of their fate. We observed that electroporation of Olig3 and Ptf1a expression vectors, but not either alone, induced Foxd3. We therefore propose that Olig3 can cooperate with Ptf1a to determine the fate of climbing fiber neurons of the inferior olivary nucleus.
Olig3基因编码一种bHLH因子,该因子在后脑背侧翼板的脑室区表达。我们发现,Olig3(+)祖细胞结构域包含共表达Math1、Ngn1、Mash1和Ptf1a的子结构域。Olig3(+)细胞产生我们称为A类神经元的背侧翼板中的神经元类型。我们使用遗传谱系追踪来证明A类神经元对孤束核和小脑前核有贡献。在Olig3突变小鼠中,A类神经元的命运没有被正确确定。结果,孤束核没有形成,并且小脑前核,如下橄榄核,缺失或很小。以A类神经元为代价,异位的Lbx1(+)神经元出现在Olig3突变小鼠的翼板中。相比之下,在鸡后脑中电穿孔Olig3表达载体可抑制Lbx1(+)神经元的出现。下橄榄核的攀缘纤维神经元表达Foxd3,并且其命运的确定需要Olig3以及Ptf1a。我们观察到,电穿孔Olig3和Ptf1a表达载体,但不是单独电穿孔其中任何一个,可诱导Foxd3。因此,我们提出Olig3可以与Ptf1a合作来确定下橄榄核攀缘纤维神经元的命运。