Cerebral cortex projection neurons (PNs) are generated from intermediate progenitors (IPs), which are in turn derived from radial glial progenitors (RGPs). To investigate developmental processes in IPs, we profiled IP transcriptomes in embryonic mouse neocortex, using transgenic Tbr2-GFP mice, cell sorting, and microarrays. These data were used in combination with in situ hybridization to ascertain gene sets specific for IPs, RGPs, PNs, interneurons, and other neural and non-neural cell types. RGP-selective transcripts (n=419) included molecules for Notch receptor signaling, proliferation, neural stem cell identity, apical junctions, necroptosis, hippo pathway, and NF-κB pathway. RGPs also expressed specific genes for critical interactions with meningeal and vascular cells. In contrast, IP-selective genes (n=136) encoded molecules for activated Delta ligand presentation, epithelial-mesenchymal transition, core planar cell polarity (PCP), axon genesis, and intrinsic excitability. Interestingly, IPs expressed several "dependence receptors" (Unc5d, Dcc, Ntrk3, Epha4) that induce apoptosis in the absence of ligand, suggesting a competitive mechanism for IPs and new PNs to detect key environmental cues or die. Overall, our results imply a novel role for IPs in the patterning of neuronal polarization, axon differentiation, and intrinsic excitability prior to mitosis. Significantly, IPs highly express Wnt-PCP, netrin, and semaphorin pathway molecules known to regulate axon polarization in other systems. In sum, IPs not only amplify neurogenesis quantitatively, but also molecularly "prime" new PNs for axogenesis, guidance, and excitability.

中文翻译：

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小鼠新皮质发育中的细胞类型特异性基因表达：与轴突发育有关的中间祖细胞

大脑皮层投射神经元 (PN) 由中间祖细胞 (IP) 生成，而中间祖细胞又源自放射状胶质祖细胞 (RGP)。为了研究 IP 的发育过程，我们使用转基因 Tbr2-GFP 小鼠、细胞分选和微阵列分析了胚胎小鼠新皮质中的 IP 转录组。这些数据与原位杂交结合使用，以确定特定于 IP、RGP、PN、中间神经元和其他神经和非神经细胞类型的基因组。RGP 选择性转录本 (n=419) 包括用于 Notch 受体信号传导、增殖、神经干细胞特性、顶端连接、坏死性凋亡、河马通路和 NF-κB 通路的分子。RGPs 还表达了与脑膜和血管细胞关键相互作用的特定基因。相比之下，IP 选择性基因 (n=136) 编码激活 Delta 配体呈递、上皮间质转化、核心平面细胞极性 (PCP)、轴突发生和内在兴奋性的分子。有趣的是，IPs 表达了几种“依赖受体”（Unc5d、Dcc、Ntrk3、Epha4），它们在没有配体的情况下诱导细胞凋亡，这表明 IPs 和新 PNs 检测关键环境线索或死亡的竞争机制。总体而言，我们的研究结果表明 IP 在有丝分裂前的神经元极化、轴突分化和内在兴奋性模式中具有新的作用。重要的是，IP 高度表达 Wnt-PCP、netrin 和信号素通路分子，这些分子已知可调节其他系统中的轴突极化。总而言之，IPs 不仅在数量上放大了神经发生，而且在分子上“启动”了新的 PNs 用于轴发生，