神经元的大小,形成新生儿大脑皮层的星形胶质细胞和少突胶质细胞补体在很大程度上取决于胶质干细胞产生谱系定向祖细胞的速率,而后者发展为成熟细胞类型。这里,我们调查了pallial干细胞\'(SCs)对星型发生的空间衔接以及定向星形胶质细胞祖细胞(APs)向分化星形胶质细胞的进展,通过对苍白前体的克隆和动力学分析。我们发现尾内侧(CM)SCs比rostro外侧(RL)SCs更容易发生星象,而RL承诺的AP比CM更热衷于扩散。接下来,我们通过2个关键转录因子基因掌握早期皮质原基的区域化来评估这些现象的控制,Emx2和Foxg1,通过慢病毒体细胞转基因,上位性测定,和临时救援试验。我们证明了Emx2主要通过Couptf1、Nfia、和Sox9上调,虽然Foxg1在某种程度上拮抗了这种进展,可能是通过Zbtb20的镇压。最后,我们发现Foxg1和Emx2可能不对称地和对立地参与了海马和新皮层AP表现出的独特增殖/分化行为的形成。
Sizes of neuronal, astroglial and oligodendroglial complements forming the neonatal cerebral cortex largely depend on rates at which pallial stem cells give rise to lineage-committed progenitors and the latter ones progress to mature cell types. Here, we investigated the spatial articulation of pallial stem cells\' (SCs) commitment to
astrogenesis as well as the progression of committed astroglial progenitors (APs) to differentiated astrocytes, by clonal and kinetic profiling of pallial precursors. We found that caudal-medial (CM) SCs are more prone to
astrogenesis than rostro-lateral (RL) ones, while RL-committed APs are more keen to proliferate than CM ones. Next, we assessed the control of these phenomena by 2 key transcription factor genes mastering regionalization of the early cortical primordium, Emx2 and Foxg1, via lentiviral somatic transgenesis, epistasis assays, and ad hoc rescue assays. We demonstrated that preferential CM SCs progression to
astrogenesis is promoted by Emx2, mainly via Couptf1, Nfia, and Sox9 upregulation, while Foxg1 antagonizes such progression to some extent, likely via repression of Zbtb20. Finally, we showed that Foxg1 and Emx2 may be implicated-asymmetrically and antithetically-in shaping distinctive proliferative/differentiative behaviors displayed by APs in hippocampus and neocortex.