Greig Luciano C, Woodworth Mollie B, Greppi Chloé, Macklis Jeffrey D
Department of Stem Cell and Regenerative Biology, Center for Brain Science and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02215, USA.
Department of Stem Cell and Regenerative Biology, Center for Brain Science and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02215, USA.
Neuron. 2016 Apr 20;90(2):261-77. doi: 10.1016/j.neuron.2016.03.008.
While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive "sensory field" in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development.
虽然已经确定了对皮质区域大小和相对位置的转录控制,但对于指导区域特异性特征获得的调节因子了解较少。在这里,我们报告转录因子Ctip1在初级感觉区域发挥作用,抑制运动相关基因表达并激活感觉相关基因表达程序,从而建立起界定功能区域的清晰分子边界。在Ctip1突变体中,异常的基因表达导致皮质-皮质和皮质-传出输出连接异常地向运动方向发展。Ctip1对IV层神经元的分化起关键调节作用,皮质中Ctip1的选择性缺失使丘脑皮质轴突在IV层失去其接受性“感觉场”,该感觉场通常提供一个由切线和径向定义的专用突触区域隔室。因此,尽管丘脑皮质轴突侵入了适当的皮质区域,但它们无法组织成正确配置的感觉图谱。这些数据共同确定Ctip1是感觉区域发育的关键控制因素。