Fhod3 Controls the Dendritic Spine Morphology of Specific Subpopulations of Pyramidal Neurons in the Mouse Cerebral Cortex
Fhod3 Controls the Dendritic Spine Morphology of Specific Subpopulations of Pyramidal Neurons in the Mouse Cerebral Cortex
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Fhod3 控制小鼠大脑皮层锥体神经元特定亚群的树突棘形态
DOI：
10.1093/cercor/bhaa355
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Takeya Ryu
中科院分区：
文献类型：
--
作者：
Sulistomo Hikmawan Wahyu;Nemoto Takayuki;Kage Yohko;Fujii Hajime;Uchida Taku;Takamiya Kogo;Sumimoto Hideki;Kataoka Hiroaki;Bito Haruhiko;Takeya Ryu
树突棘的形状和大小的变化对突触传递至关重要。这些形态学变化依赖于肌动蛋白细胞骨架的动态组装，并且在不同类型的神经元中发生不同。然而，肌动蛋白动力学如何在神经元细胞类型特异性的方式进行调节仍然在很大程度上未知。我们发现，FHOD 3，一个成员的cardiac家族蛋白质介导的F-肌动蛋白组装，控制树突棘形态发生的特定亚群的皮质锥体神经元。Fhod 3在小鼠大脑皮层限制区域的II/III和V层内的兴奋性锥体神经元中特异性表达。免疫组织化学和生物化学分析显示Fhod 3在突触后棘中积累。尽管在脑中靶向缺失Fhod 3不会导致脑的大体或组织学外观的任何缺陷，但在假定的Fhod 3阳性区域内的锥体神经元中的树突棘在形态上异常。在从Fhod 3耗尽皮质制备的原代培养物中，仅在Fhod 3启动子活性细胞中检测到棘形态缺陷，这是一小群锥体神经元，而在Fhod 3启动子阴性锥体神经元中未检测到。因此，Fhod 3在树突棘形态发生中仅以细胞类型特异性方式在特定的锥体神经元群体中起关键作用。
Changes in the shape and size of the dendritic spines are critical for synaptic transmission. These morphological changes depend on dynamic assembly of the actin cytoskeleton and occur differently in various types of neurons. However, how the actin dynamics are regulated in a neuronal cell type-specific manner remains largely unknown. We show that Fhod3, a member of the formin family proteins that mediate F-actin assembly, controls the dendritic spine morphogenesis of specific subpopulations of cerebrocortical pyramidal neurons. Fhod3 is expressed specifically in excitatory pyramidal neurons within layers II/III and V of restricted areas of the mouse cerebral cortex. Immunohistochemical and biochemical analyses revealed the accumulation of Fhod3 in postsynaptic spines. Although targeted deletion of Fhod3 in the brain did not lead to any defects in the gross or histological appearance of the brain, the dendritic spines in pyramidal neurons within presumptive Fhod3-positive areas were morphologically abnormal. In primary cultures prepared from the Fhod3-depleted cortex, defects in spine morphology were only detected inFhod3promoter-active cells, a small population of pyramidal neurons, and not inFhod3promoter-negative pyramidal neurons. Thus, Fhod3 plays a crucial role in dendritic spine morphogenesis only in a specific population of pyramidal neurons in a cell type-specific manner.