Integrin β3 organizes dendritic complexity of cerebral cortical pyramidal neurons along a tangential gradient.
Integrin β3 organizes dendritic complexity of cerebral cortical pyramidal neurons along a tangential gradient.
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DOI：
10.1186/s13041-020-00707-0
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发表时间：
2020-12-14
期刊：
影响因子：
3.6
通讯作者：
Vidal GS
中科院分区：
文献类型：
--
作者：
Swinehart BD;Bland KM;Holley ZL;Lopuch AJ;Casey ZO;Handwerk CJ;Vidal GS
功能障碍性树突分支是许多发育性神经系统疾病的关键特征。在不同的人脑区域，基底树突的复杂性是已知的增加沿着尾侧到喙侧的梯度。我们最近发现，小鼠第II/III层皮质锥体神经元的基底树突复杂性沿着横跨多个区域的尾内侧到头外侧梯度沿着增加，但当时还没有已知的分子来调节这种精致的模式。整合素亚基与树突发育有关，与自闭症谱系障碍和智力残疾相关性最强的亚基是整合素β3（Itgb 3）。在小鼠中，Itgb 3的整体敲除导致自闭症样神经解剖学和行为。在这里，我们测试的假设，Itgb 3是需要增加树突的复杂性沿着最近发现的切向梯度层II/III皮质锥体神经元。我们通过Cre-loxP介导的Itgb 3切除针对Itgb 3功能丧失的II/III层皮质锥体神经元的子集。我们追踪了靶神经元的喙尾侧和中外侧位置，并重建了它们的树突。与对照组相比，Itgb 3突变神经元的基础树突复杂性与其皮质位置无关。突变体和对照神经元的基础树突复杂性不同，因为多个分支顺序（初级，次级等）的分支数量总体变化，而不是在那些分支级处的平均长度的任何变化。此外，树突棘密度与皮质位置在控制，但不是突变神经元。因此，孤独症易感基因Itgb 3是建立第二/第三层皮质锥体神经元之间的基底树突复杂性的切线模式所必需的，这表明该分子在发育中的大脑中的早期作用。
Dysfunctional dendritic arborization is a key feature of many developmental neurological disorders. Across various human brain regions, basal dendritic complexity is known to increase along a caudal-to-rostral gradient. We recently discovered that basal dendritic complexity of layer II/III cortical pyramidal neurons in the mouse increases along a caudomedial-to-rostrolateral gradient spanning multiple regions, but at the time, no molecules were known to regulate that exquisite pattern. Integrin subunits have been implicated in dendritic development, and the subunit with the strongest associations with autism spectrum disorder and intellectual disability is integrin β3 (Itgb3). In mice, global knockout of Itgb3 leads to autistic-like neuroanatomy and behavior. Here, we tested the hypothesis that Itgb3 is required for increasing dendritic complexity along the recently discovered tangential gradient among layer II/III cortical pyramidal neurons. We targeted a subset of layer II/III cortical pyramidal neurons for Itgb3 loss-of-function via Cre-loxP-mediated excision of Itgb3. We tracked the rostrocaudal and mediolateral position of the targeted neurons and reconstructed their dendritic arbors. In contrast to controls, the basal dendritic complexity of Itgb3 mutant neurons was not related to their cortical position. Basal dendritic complexity of mutant and control neurons differed because of overall changes in branch number across multiple branch orders (primary, secondary, etc.), rather than any changes in the average length at those branch orders. Furthermore, dendritic spine density was related to cortical position in control but not mutant neurons. Thus, the autism susceptibility gene Itgb3 is required for establishing a tangential pattern of basal dendritic complexity among layer II/III cortical pyramidal neurons, suggesting an early role for this molecule in the developing brain.
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影响因子：
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Finlay BL
影响因子：
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de Anda, Froylan Calderon;Rosario, Ana Lucia;Durak, Omer;Tran, Tracy;Graeff, Johannes;Meletis, Konstantinos;Rei, Damien;Soda, Takahiro;Madabhushi, Ram;Ginty, David D.;Kolodkin, Alex L.;Tsai, Li-Huei
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