Nat. Commun.：影响神经祖细胞分化的关键因子

了解神经干细胞的分化过程和神经前体细胞的命运决定对于再生医学领域有重要的意义。

在神经系统发育的过程中，神经祖细胞既要维持自我更新，又要分化成各种类型的神经细胞，而这种分化与自我更新之间的平衡是依靠多种生长因子协同作用来完成的。例如，在端脑，Shh(sonic hedgehog)途径能够启动神经祖细胞的自我更新、抑制终末分化。与之相反的是，RA(retinoic acid，维甲酸)能够促进分化、抑制神经祖细胞的增殖。但是，这些生长因子之间是如何协同合作，使神经系统正常发育的，目前尚不清楚。

Nkx2.1是决定皮层中间神经元亚型的转录因子。它规定了内侧神经嵴（MGE）中神经母细胞的身份。Nkx2.1低表达的细胞趋向于迁移到皮层，而Nkx2.1高表达的细胞则会迁移到纹状体。而Nkx2.1正是Shh途径的一个靶蛋白。

本文中，研究人员通过将胚胎干细胞诱导分化成神经细胞来模拟正常的神经系统发生过程。发现了一种叫做Activin (激活素)的潜在神经营养因子，在诱导神经细胞分化中起着关键作用。Activin通过抑制Shh途径和增强RA途径使细胞退出有丝分裂周期，进入分化。

此外，研究人员还发现，Activin 能够通过Shh途径来影响Nkx2.1的表达，从而决定了这些神经前体细胞的迁移方向，以及它们会发育成哪种亚型的皮层中间神经元。（生物谷 Bioon.com  ）

doi:10.1038/ncomms1817
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Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors

Serafí Cambray, Charles Arber, Graham Little, Antonios G. Dougalis, Vincenzo de Paola, Mark A. Ungless, Meng Li & Tristan A. Rodríguez

Understanding the mechanisms underlying neural progenitor differentiation and neuronal fate specification is critical for the use of embryonic stem cells (ESCs) for regenerative medicine. Cortical interneurons are of particular interest for cell transplantation; however, only a limited subset of these neurons can be generated from ESCs. Here we uncover a pivotal role for Activin in regulating the differentiation and identity of telencephalic neural precursors derived from mouse and human ESCs. We show that Activin directly inhibits the mitogenic sonic hedgehog pathway in a Gli3-dependent manner while enhancing retinoic acid signalling, the pro-neurogenic pathway. In addition, we demonstrate that Activin provides telencephalic neural precursors with positional cues that specifically promote the acquisition of a calretinin interneuron fate by controlling the expression of genes that regulate cortical interneuron identity. This work demonstrates a novel means for regulating neuronal differentiation and specification of subtype identity.