Department of Anatomy, School of Medicine, Keio University Tokyo, Japan ; Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center Kasugai, Japan.
Front Neuroanat. 2013 Jul 31;7:24. doi: 10.3389/fnana.2013.00024. eCollection 2013.
During neocortical development, excitatory neurons are produced from apical progenitors in the ventricular zone (VZ) or from dividing cells in the subventricular zone (SVZ). We previously reported that the direct progenies of VZ cells in mice slowly exit the VZ and accumulate just above the VZ (lower SVZ) as multipolar migrating neurons, whereas subsequently dividing cells in the SVZ exit the VZ earlier than the former and become widely distributed in the SVZ. These two populations are named the slowly exiting population (SEP) and the rapidly exiting population (REP), respectively. In mice, REP cells include basal progenitors as the major population and are characterized by a long ascending process; their morphology resembles that of basal radial glial cells (bRGs), which have been observed in the inner and outer SVZ in primates. The dramatic increase in the number of bRGs in primates, especially in humans, is thought to underlie the acquisition of a huge cortex during evolution. We previously reported that the REP/SEP production rate in the lateral cortical VZ is higher than that in the dorsomedial VZ in mice. To search for molecules responsible for the higher REP production in the lateral cortical VZ, we conducted microarray analyses and identified genes that were differentially expressed between the lateral and medial VZs in mice. These genes were considered to be among the candidates responsible for the regulation of the REP/SEP production rate. To investigate the selection pressures during primate evolution on these candidate genes, we estimated the synonymous vs. non-synonymous base substitution rates. As a result, the negative selection pressures on the Megf11, Dmrt3, and Cntn3 genes were found to be significantly weaker in primates than in non-primates, while those on Jag1, Ntrk2, and Pmp22 were stronger. Candidate molecules responsible for primate cortical expansion through an increase in bRGs may be included among these genes.
在新皮层发育过程中，兴奋性神经元由室管膜下区 (SVZ) 中的顶祖细胞或分裂细胞产生。我们之前报道过，小鼠室管膜下区细胞的直接后代缓慢离开室管膜下区并积聚在室管膜下区上方（下 SVZ）作为多极迁移神经元，而随后 SVZ 中的分裂细胞比前者更早离开室管膜下区，并广泛分布在 SVZ 中。这两个群体分别被命名为缓慢退出群体 (SEP) 和快速退出群体 (REP)。在小鼠中，REP 细胞包括作为主要群体的基底祖细胞，其特征是具有长的上升过程；它们的形态类似于在灵长类动物的内外 SVZ 中观察到的基底放射状胶质细胞 (bRG)。灵长类动物中 bRG 数量的急剧增加，尤其是在人类中，被认为是进化过程中大脑皮层获得巨大发展的基础。我们之前报道过，在小鼠中，外侧皮质 VZ 的 REP/SEP 产生率高于背内侧 VZ。为了寻找负责外侧皮质 VZ 中 REP 产生较高的分子，我们进行了微阵列分析，并鉴定出在小鼠中侧脑室和中脑室之间差异表达的基因。这些基因被认为是负责调节 REP/SEP 产生率的候选基因之一。为了研究这些候选基因在灵长类动物进化过程中的选择压力，我们估计了同义与非同义碱基取代率。结果表明，Megf11、Dmrt3 和 Cntn3 基因在灵长类动物中的负选择压力明显低于非灵长类动物，而 Jag1、Ntrk2 和 Pmp22 的负选择压力更强。通过增加 bRG 来扩大皮质的候选分子可能包含在这些基因中。
