BACKGROUND The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment. MAIN BODY Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-β signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-β, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD. CONCLUSION The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods.

中文翻译：

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自闭症谱系障碍的神经发育途径受损：信号传导机制和串扰的回顾。

背景技术自闭症谱系障碍（ASD）的病因中涉及多种遗传和非遗传因素可以证明自闭症大脑的发展是一个高度复杂的过程。尽管是多因素神经发育障碍，自闭症患者仍表现出一些关键特征，例如社交互动受损和重复行为增多，表明在ASD大脑发育过程中，异常信号通路引起了特定神经元回路的紊乱。对自闭症信号传导机制和相互作用的全面综述可提供对ASD病因和治疗的更好理解。主要身体对遗传模型和具有几种不同突变基因的ASD患者的最新研究表明，WNT，BMP，SHH，和视黄酸（RA）信号。尽管到目前为止，尚无关于ASD中FGF或TGF-β信号功能异常的直接证据，但可以找到一些间接证据的例子。这篇综述文章总结了据报道导致ASD的各种遗传和非遗传因素如何与WNT，BMP /TGF-β，SHH，FGF和RA信号通路相互作用。据报道自闭症相关基因泛素蛋白连接酶E3A（UBE3A）影响WNT，BMP和RA信号通路，提示自闭症大脑发育过程中各种信号通路之间存在串扰。最后，本文评论了可以进行哪些进一步的研究，以更深入地了解ASD病因中受干扰的信号传导途径。