两种FOXP转录因子之间的补偿维持了正确的条状状细胞功能
Newaz I Ahmed1,2, Nitin Khandelwal1,2, Ashley G Anderson1,3,4
1Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390-9111, USA.
bioRxiv : the preprint server for biology
|July 10, 2023
概括
在多巴胺受体1 (D1) 棘状投射神经元 (SPNs) 中失去Foxp1和Foxp2会损害运动和社会行为. 恢复Foxp1功能改善了这些缺陷,揭示了神经发育中的互补作用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 条形体中的棘状投射神经元 (SPN) 对于运动控制和奖励处理至关重要.
- 在SPN中转录因子的突变与神经发育障碍 (NDD) 有关.
- 福克斯p1和福克斯p2是D1-SPNs表达的类似的转录因子,已知与NDDs有联系.
研究的目的:
- 研究Foxp1和Foxp2在D1-SPN中的作用.
- 了解这些基因的丧失如何影响行为和神经元功能.
- 探索基因修复的潜力,以纠正缺陷.
主要方法:
- 具有D1-SPN特定损失Foxp1,Foxp2或两者的小鼠的世代.
- 行为评估 (运动和社会).
- 电生理学来测量神经元的发射.
- 细胞类型特定的基因组分析 (差异基因表达).
- 病毒介导的Foxp1.1的重新表达.
主要成果:
- 在D1-SPN中,Foxp1和Foxp2的损失导致了运动和社会行为障碍.
- D1-SPNs在双重淘汰的小鼠中显示出更高的射击率.
- 基因表达分析揭示了与自闭症风险,电生理学和神经元发育相关的基因的变化.
- 在双重淘汰赛中,Foxp1的重新表达恢复了正常的电生理和行为功能.
结论:
- 在D1-SPN中,Foxp1和Foxp2具有互补的作用.
- 这些转录因子对于正常的运动和社会行为至关重要.
- 由Foxp1/Foxp2损失引起的缺陷可以通过恢复Foxp1表达来挽救.
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