Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Nat Neurosci. 2014 Aug;17(8):1046-54. doi: 10.1038/nn.3757. Epub 2014 Jul 6.
The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of subtype-specific and pan-neuronal genes. The regulatory logic that orchestrates the expression of these unique combinations of genes is unknown for any class of cortical neuron. Here, we report that Fezf2 is a selector gene able to regulate the expression of gene sets that collectively define mouse corticospinal motor neurons (CSMN). We find that Fezf2 directly induces the glutamatergic identity of CSMN via activation of Vglut1 (Slc17a7) and inhibits a GABAergic fate by repressing transcription of Gad1. In addition, we identify the axon guidance receptor EphB1 as a target of Fezf2 necessary to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtype-specific and pan-neuronal gene batteries by a single transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity.
新皮层包含无与伦比的神经元亚型多样性，每种亚型都由发育过程中受特定亚型和全神经元基因控制的独特特征定义。目前还不知道调控这些独特基因组合表达的调控逻辑。在这里，我们报告说 Fezf2 是一个选择基因，能够调节一组基因的表达，这些基因共同定义了小鼠皮质脊髓运动神经元 (CSMN)。我们发现，Fezf2 通过激活 Vglut1（Slc17a7）直接诱导 CSMN 的谷氨酸能特性，并通过抑制 Gad1 的转录来抑制 GABA 能命运。此外，我们确定轴突导向受体 EphB1 是 Fezf2 的一个靶标，对于执行皮质脊髓束的同侧延伸是必需的。我们的数据表明，单个转录因子对神经元亚型特异性和全神经元基因电池的共同调控表达是负责建立 CSMN 特性的调控逻辑的一个组成部分。
