Iyer Asha, Vaasjo Lee O, Siththanandan Verl B, K C Rajan, Thurmon Abbigail, Akumuo Mauren, Lu Victoria, Nnebe Chelsea, Nair Ramesh, Galazo Maria J, Tharin Suzanne
Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
Neuroscience program, Tulane Brain Institute, Tulane University, New Orleans, LA 70118 USA.
iScience. 2024 Nov 28;27(12):111500. doi: 10.1016/j.isci.2024.111500. eCollection 2024 Dec 20.
Different neuron types develop characteristic axonal and dendritic arborizations that determine their inputs, outputs, and functions. Expression of fate-determinant transcription factors is essential for specification of their distinct identities. However, the mechanisms downstream of fate-determinant factors coordinating different aspects of neuron identity are not understood. Specifically, how distinct projection neurons develop appropriate dendritic arbors that determine their inputs is unknown. Here, we investigate this question in corticospinal and callosal projection neurons. We identified a mechanism linking the corticospinal/corticofugal identity gene with the regulation of dendritic development. We show that miR-193b∼365 microRNA cluster is regulated by and enriched in corticospinal neurons. miR-193b∼365 represses mitogen-activated protein kinase 8 (MAPK8) to regulate corticospinal dendritic development. miR-193b∼365 overexpression in callosal neurons abnormally reduces MAPK8 signal and dendritic complexity. Our findings show that regulation of MAPK8 via miR-193b∼365 cluster regulates dendritic development, providing a mechanism that coordinates projection neuron identity, specified by , and neuron-specific dendritic morphology.
不同类型的神经元会形成独特的轴突和树突分支，这些分支决定了它们的输入、输出和功能。命运决定转录因子的表达对于确定它们的不同身份至关重要。然而，命运决定因子下游协调神经元身份不同方面的机制尚不清楚。具体而言，不同的投射神经元如何形成决定其输入的合适树突分支尚不清楚。在这里，我们在皮质脊髓和胼胝体投射神经元中研究这个问题。我们确定了一种将皮质脊髓/皮质离心身份基因与树突发育调节联系起来的机制。我们表明，miR-193b∼365微小RNA簇受皮质脊髓神经元调控并在其中富集。miR-193b∼365抑制丝裂原活化蛋白激酶8（MAPK8）以调节皮质脊髓树突发育。在胼胝体神经元中过表达miR-193b∼365会异常降低MAPK8信号和树突复杂性。我们的研究结果表明，通过miR-193b∼365簇对MAPK8的调节可调控树突发育，提供了一种协调由[未提及的因子]指定的投射神经元身份和神经元特异性树突形态的机制。
