Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Mol Cell Neurosci. 2013 May;54:58-70. doi: 10.1016/j.mcn.2013.01.002. Epub 2013 Jan 22.
Tracking olfactory bulb mitral cell development with BrdU labeling, we find that mitral cells are generated from Pax6+ radial glial cells in the ventricular zone of the embryonic olfactory bulb. Unlike cortical projection neurons, postmitotic mitral cell precursors express both Tbr1 and Tbr2. Our tracking experiments revealed that down-regulation of Pax6 preceded up-regulation of Tbrs, and that Tbr1 emerged earlier than Tbr2. Using in utero electroporation, we also show that Pax6 negatively regulates the expression of Tbr1 and Tbr2 in postmitotic mitral cell precursors. Exogenous expression of Pax6 in embryonic olfactory bulb postmitotic precursors decreased the number of cells that progressed to a mitral cell fate. In contrast, exogenous expression of Pax6 resulted in an increase of GABAergic and/or dopaminergic interneurons. These results indicate that Pax6 is a regulator of fate determination of precursor cells.
通过 BrdU 标记追踪嗅球僧帽细胞的发育,我们发现僧帽细胞是由胚胎嗅球室管膜区的 Pax6+放射状胶质细胞产生的。与皮质投射神经元不同,有丝分裂后僧帽细胞前体细胞同时表达 Tbr1 和 Tbr2。我们的追踪实验表明,Pax6 的下调先于 Tbr 的上调,而且 Tbr1 的出现早于 Tbr2。通过体内电穿孔,我们还表明 Pax6 负调控有丝分裂后僧帽细胞前体细胞中 Tbr1 和 Tbr2 的表达。胚胎嗅球有丝分裂后前体细胞中 Pax6 的异位表达减少了向僧帽细胞命运分化的细胞数量。相比之下,Pax6 的异位表达导致 GABA 能和/或多巴胺能中间神经元的增加。这些结果表明 Pax6 是前体细胞命运决定的调节因子。