The role of cerebellar FOXP1 in the development of motor and communicative behaviors in mice

IF 2.4 4区 心理学 Q2 BEHAVIORAL SCIENCES
R. Chasse, R. McLeod, A. Surian, R. H. Fitch, J. Li
{"title":"The role of cerebellar FOXP1 in the development of motor and communicative behaviors in mice","authors":"R. Chasse,&nbsp;R. McLeod,&nbsp;A. Surian,&nbsp;R. H. Fitch,&nbsp;J. Li","doi":"10.1111/gbb.70001","DOIUrl":null,"url":null,"abstract":"<p>The gene <i>FOXP2</i> is well established for a role in human speech and language; far less is known about <i>FOXP1</i>. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum—a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock-out of <i>Foxp1</i> using an <i>En1-Cre</i> driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic-relevant behaviors. Male and female mice with a conditional knock-out (cKO, <i>n</i> = 31) and wildtype littermate controls (WT, <i>n</i> = 34) were assessed for gross and orofacial motor control, motor-coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest <i>Foxp1</i> plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of <i>Foxp1</i> in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70001","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes Brain and Behavior","FirstCategoryId":"102","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gbb.70001","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

The gene FOXP2 is well established for a role in human speech and language; far less is known about FOXP1. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum—a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock-out of Foxp1 using an En1-Cre driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic-relevant behaviors. Male and female mice with a conditional knock-out (cKO, n = 31) and wildtype littermate controls (WT, n = 34) were assessed for gross and orofacial motor control, motor-coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest Foxp1 plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of Foxp1 in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans.

小脑 FOXP1 在小鼠运动和交流行为发育中的作用
FOXP2 基因在人类言语和语言中的作用已得到公认,但人们对 FOXP1 的了解却少得多。不过,这一相关基因也与人类语言发育以及与自闭症谱系障碍(ASD)特征相关的疾病有关。最近在小脑中也发现了 FOXP1 蛋白的表达--这种神经结构以前曾被证明表达 FOXP2 蛋白。En1-Cre驱动程序在整个小脑以及中脑和脊髓的神经元亚群中都很活跃,本研究试图利用包括与小脑功能障碍相关的运动任务以及与交流和自闭症相关的行为在内的一系列测试,阐明使用En1-Cre驱动程序有条件敲除Foxp1对小鼠行为的影响。对条件性基因敲除(cKO,n = 31)的雄性和雌性小鼠以及野生型同窝对照(WT,n = 34)进行了粗大和口面部运动控制、运动协调学习、运动、社交行为、焦虑、听觉处理和表达性发声的评估。总体结果表明,Foxp1在交流系统的发育过程中扮演着特殊的角色,其表型表现可能与性别有关。与 Foxp1 蛋白缺失相关的运动障碍可能会特别影响发声,而 cKO 受试者显著的口面部运动障碍也可能导致发声异常。总之,目前的研究为了解 Foxp1 在小鼠小脑功能和相关行为中的作用提供了重要线索,对更好地理解人类的交流和基于运动的神经发育障碍具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Genes Brain and Behavior
Genes Brain and Behavior 医学-行为科学
CiteScore
6.80
自引率
4.00%
发文量
62
审稿时长
4-8 weeks
期刊介绍: Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信