National Institute for Medical Research (NIMR), Medical Research Council (MRC), Department of Molecular Neurobiology, London NW7 1AA, UK.
Development. 2010 Jan;137(2):293-302. doi: 10.1242/dev.041178.
Cajal-Retzius (CR) cells play a key role in the formation of the cerebral cortex. These pioneer neurons are distributed throughout the cortical marginal zone in distinct graded distributions. Fate mapping and cell lineage tracing studies have recently shown that CR cells arise from restricted domains of the pallial ventricular zone, which are associated with signalling centres involved in the early regionalisation of the telencephalic vesicles. In this study, we identified a subpopulation of CR cells in the rostral telencephalon that expresses Er81, a downstream target of Fgf8 signalling. We investigated the role of the rostral telencephalic patterning centre, which secretes FGF molecules, in the specification of these cells. Using pharmacological inhibitors and genetic inactivation of Fgf8, we showed that production of Fgf8 by the rostral telencephalic signalling centre is required for the specification of the Er81+ CR cell population. Moreover, the analysis of Fgf8 gain-of-function in cultivated mouse embryos and of Emx2 and Gli3 mutant embryos revealed that ectopic Fgf8 signalling promotes the generation of CR cells with a rostral phenotype from the dorsal pallium. These data showed that Fgf8 signalling is both required and sufficient to induce rostral CR cells. Together, our results shed light on the mechanisms specifying rostral CR cells and further emphasise the crucial role of telencephalic signalling centres in the generation of distinct CR cell populations.
Cajal-Retzius (CR) 细胞在大脑皮层的形成中起着关键作用。这些先驱神经元分布在皮质边缘区，呈明显的梯度分布。命运图谱和细胞谱系追踪研究最近表明，CR 细胞起源于脑室区的特定区域，这些区域与参与端脑泡早期区域化的信号中心有关。在这项研究中，我们在端脑的前部鉴定出了一个表达 Er81 的 CR 细胞亚群，Er81 是 Fgf8 信号的下游靶标。我们研究了头部端脑模式形成中心在这些细胞特化中的作用，该中心分泌 FGF 分子。通过使用药理学抑制剂和 Fgf8 的基因失活，我们表明头部端脑信号中心产生的 Fgf8 对于 Er81+CR 细胞群体的特化是必需的。此外，对培养的小鼠胚胎中 Fgf8 获得性功能的分析以及 Emx2 和 Gli3 突变体胚胎的分析表明，异位 Fgf8 信号促进了来自背侧皮质的具有前部表型的 CR 细胞的产生。这些数据表明，Fgf8 信号对于诱导前部 CR 细胞是必需和充分的。总之，我们的研究结果揭示了指定前部 CR 细胞的机制，并进一步强调了端脑信号中心在产生不同 CR 细胞群体中的关键作用。
