Sessa Alessandro, Mao Chai-An, Hadjantonakis Anna-Katerina, Klein William H, Broccoli Vania
Molecular Neuropathology Laboratory, SCRI, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Neuron. 2008 Oct 9;60(1):56-69. doi: 10.1016/j.neuron.2008.09.028.
T-brain gene-2 (Tbr2) is specifically expressed in the intermediate (basal) progenitor cells (IPCs) of the developing cerebral cortex; however, its function in this biological context has so far been overlooked due to the early lethality of Tbr2 mutant embryos. Conditional ablation of Tbr2 in the developing forebrain resulted in the loss of IPCs and their differentiated progeny in mutant cortex. Intriguingly, early loss of IPCs led to a decrease in cortical surface expansion and thickness with a neuronal reduction observed in all cortical layers. These findings suggest that IPC progeny contribute to the correct morphogenesis of each cortical layer. Our observations were confirmed by tracing Tbr2+ IPC cell fate using Tbr2::GFP transgenic mice. Finally, we demonstrated that misexpression of Tbr2 is sufficient to induce IPC identity in ventricular radial glial cells (RGCs). Together, these findings identify Tbr2 as a critical factor for the specification of IPCs during corticogenesis.
T脑基因2（Tbr2）在发育中的大脑皮层的中间（基底）祖细胞（IPC）中特异性表达；然而，由于Tbr2突变胚胎的早期致死性，其在这种生物学背景下的功能至今被忽视。在发育中的前脑有条件地敲除Tbr2导致突变皮层中IPC及其分化后代的缺失。有趣的是，IPC的早期缺失导致皮质表面扩张和厚度减小，且在所有皮质层均观察到神经元减少。这些发现表明，IPC后代有助于每个皮质层的正确形态发生。我们的观察结果通过使用Tbr2::GFP转基因小鼠追踪Tbr2+ IPC细胞命运得到证实。最后，我们证明Tbr2的错误表达足以在室管膜放射状胶质细胞（RGC）中诱导IPC特性。总之，这些发现确定Tbr2是皮质发生过程中IPC特化的关键因子。
