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FOXP 转录因子在脊椎动物大脑发育、功能和疾病中的作用。

FOXP transcription factors in vertebrate brain development, function, and disorders.

机构信息

Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon.

Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.

出版信息

Wiley Interdiscip Rev Dev Biol. 2020 Sep;9(5):e375. doi: 10.1002/wdev.375. Epub 2020 Jan 30.

Abstract

FOXP transcription factors are an evolutionarily ancient protein subfamily coordinating the development of several organ systems in the vertebrate body. Association of their genes with neurodevelopmental disorders has sparked particular interest in their expression patterns and functions in the brain. Here, FOXP1, FOXP2, and FOXP4 are expressed in distinct cell type-specific spatiotemporal patterns in multiple regions, including the cortex, hippocampus, amygdala, basal ganglia, thalamus, and cerebellum. These varied sites and timepoints of expression have complicated efforts to link FOXP1 and FOXP2 mutations to their respective developmental disorders, the former affecting global neural functions and the latter specifically affecting speech and language. However, the use of animal models, particularly those with brain region- and cell type-specific manipulations, has greatly advanced our understanding of how FOXP expression patterns could underlie disorder-related phenotypes. While many questions remain regarding FOXP expression and function in the brain, studies to date have illuminated the roles of these transcription factors in vertebrate brain development and have greatly informed our understanding of human development and disorders. This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Nervous System Development > Vertebrates: Regional Development.

摘要

叉头框蛋白转录因子是一个进化上古老的蛋白质亚家族,在脊椎动物体内协调多个器官系统的发育。它们的基因与神经发育障碍有关,这引起了人们对其在大脑中的表达模式和功能的特别关注。在这里,FOXP1、FOXP2 和 FOXP4 在多个区域(包括皮层、海马体、杏仁核、基底神经节、丘脑和小脑)中以特定的细胞类型特异性时空模式表达。这些不同的表达部位和时间点使得将 FOXP1 和 FOXP2 突变与其各自的发育障碍联系起来的工作变得复杂,前者影响全局神经功能,后者则特别影响言语和语言。然而,利用动物模型,特别是那些具有脑区和细胞类型特异性操作的动物模型,极大地促进了我们对 FOXP 表达模式如何为相关疾病表型提供基础的理解。虽然关于 FOXP 在大脑中的表达和功能仍有许多问题有待解决,但迄今为止的研究阐明了这些转录因子在脊椎动物大脑发育中的作用,并极大地促进了我们对人类发育和疾病的理解。本文属于以下分类:神经系统发育 > 脊椎动物:一般原则基因表达和转录层次 > 基因网络和基因组学神经系统发育 > 脊椎动物:区域发育。

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