Vien Khanh M, Duan Qichen, Yeung Chun, Barish Scott, Volkan Pelin Cayirlioglu
Department of Biology, Duke University, Durham, NC 27708, USA.
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
iScience. 2024 Jun 21;27(7):110340. doi: 10.1016/j.isci.2024.110340. eCollection 2024 Jul 19.
The process of how neuronal identity confers circuit organization is intricately related to the mechanisms underlying neurodegeneration and neuropathologies. Modeling this process, the olfactory circuit builds a functionally organized topographic map, which requires widely dispersed neurons with the same identity to converge their axons into one a class-specific neuropil, a glomerulus. In this article, we identified Fat2 (also known as Kugelei) as a regulator of class-specific axon organization. In mutants, axons belonging to the highest -expressing classes present with a more severe phenotype compared to axons belonging to low -expressing classes. In extreme cases, mutations lead to neural degeneration. Lastly, we found that Fat2 intracellular domain interactors, APC1/2 (Adenomatous polyposis coli) and (Drop out), likely orchestrate the cytoskeletal remodeling required for axon condensation. Altogether, we provide a potential mechanism for how cell surface proteins' regulation of cytoskeletal remodeling necessitates identity specific circuit organization.
神经元身份如何赋予神经回路组织的过程与神经退行性变和神经病理学的潜在机制密切相关。以嗅觉回路为例模拟这一过程，它构建了一个功能上有组织的拓扑图，这需要具有相同身份的广泛分散的神经元将其轴突汇聚到一个特定类别的神经纤维网——一个嗅小球中。在本文中，我们确定了Fat2（也称为Kugelei）是特定类轴突组织的调节因子。在突变体中，与低表达类别的轴突相比，高表达类别的轴突表现出更严重的表型。在极端情况下，突变会导致神经退行性变。最后，我们发现Fat2细胞内结构域相互作用蛋白，APC1/2（腺瘤性息肉病蛋白）和Drop out，可能协调轴突凝聚所需的细胞骨架重塑。总之，我们提供了一种潜在机制，说明细胞表面蛋白对细胞骨架重塑的调节如何需要特定身份的神经回路组织。
