Centre de Biologie Intégrative (CBI), Centre de Biologie du Développement (CBD), Université de Toulouse, CNRS, UPS, 118 route de Narbonne, 31062, Toulouse, France.
BMC Dev Biol. 2020 May 13;20(1):12. doi: 10.1186/s12861-020-00215-3.
During mammalian cerebral cortex development, different types of projection neurons are produced in a precise temporal order and in stereotypical numbers. The mechanisms regulating timely generation of neocortex projection neurons and ensuring production in sufficient numbers of each neuronal identity are only partially understood.
Here, we show that ephrin-B2, a member of the Eph:ephrin cell-to-cell communication pathway, sets the neurogenic tempo in the neocortex. Indeed, conditional mutant embryos for ephrin-B2 exhibit a transient delay in neurogenesis and acute stimulation of Eph signaling by in utero injection of synthetic ephrin-B2 led to a transient increase in neuronal production. Using genetic approaches we show that ephrin-B2 acts on neural progenitors to control their differentiation in a juxtacrine manner. Unexpectedly, we observed that perinatal neuron numbers recovered following both loss and gain of ephrin-B2, highlighting the ability of neural progenitors to adapt their behavior to the state of the system in order to produce stereotypical numbers of neurons.
Altogether, our data uncover a role for ephrin-B2 in embryonic neurogenesis and emphasize the plasticity of neuronal production in the neocortex.
在哺乳动物大脑皮层发育过程中，不同类型的投射神经元以精确的时间顺序和典型的数量产生。调节新皮层投射神经元适时产生并确保每种神经元身份产生足够数量的机制仅部分被理解。
在这里，我们表明，Eph 家族细胞间通讯途径的成员 Ephrin-B2 设定了新皮层的神经发生节奏。事实上，条件性 Ephrin-B2 突变体胚胎表现出神经发生的短暂延迟，而在子宫内注射合成 Ephrin-B2 可急性刺激 Eph 信号，导致神经元产生短暂增加。通过遗传方法，我们表明 Ephrin-B2 作用于神经祖细胞以旁分泌方式控制其分化。出乎意料的是，我们观察到 Ephrin-B2 的缺失和获得后，围产期神经元数量都得到了恢复，这突出表明神经祖细胞能够适应系统状态来产生典型数量的神经元，从而具有行为可塑性。
总之，我们的数据揭示了 Ephrin-B2 在胚胎神经发生中的作用，并强调了新皮层神经元产生的可塑性。
