The RhoGEF trio functions in sculpting class specific dendrite morphogenesis in Drosophila sensory neurons.

The RhoGEF trio functions in sculpting class specific dendrite morphogenesis in Drosophila sensory neurons.
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DOI:
10.1371/journal.pone.0033634
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Cox DN
Cox DN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Iyer SC;Wang D;Iyer EP;Trunnell SA;Meduri R;Shinwari R;Sulkowski MJ;Cox DN

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作为神经系统中突触或感觉输入的主要部位,树突在处理神经元和感觉信息中发挥着重要作用。此外,类特定树突树枝化的规范对于建立神经连接和功能网络的形成至关重要。细胞骨架调节提供了在不同神经元亚型之间建立和重组树突形态的关键机制。虽然之前的研究已经确定了小 GTPases Rac 和 Rho 在介导树突形态发生中的不同作用,但对于这些基因在介导不同树突结构中的直接调节因子知之甚少。在这里,我们证明,RhoGEF Trio 对于果蝇周围神经系统 (PNS) 树突状树枝化 (da) 感觉神经元中类特异性树突形态的规范是必需的。 Trio 在所有 da 神经元亚类中表达,功能丧失分析表明 Trio 在促进各种 da 神经元亚型中的树突分支、区域覆盖和细化树突生长方面具有细胞自主功能。此外,过表达研究表明,Trio 通过 Trio GEF1 依赖的与 Rac1 的相互作用,促进高阶树突分支,包括树突丝状伪足的形成,而 Trio GEF-2 依赖的与 Rho1 的相互作用则用于限制 da 神经元中的树突延伸和高阶分支。最后,我们表明,由同源域转录因子 Cut 诱导的从头树突分支需要 Trio 活性,表明这些分子可能在介导树突形态发生的途径中发挥作用。总的来说,我们的分析表明 Trio 通过与 Rac1 和 Rho1 相互作用,作为类特异性 da 神经元树突形态发生的重要调节剂,并表明 Trio 是树突分支和丝状伪足形成的 Cut 介导调节中需要的下游效应器。
As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures. Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis. Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation.
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