Liu Yitong, Hong Wentong, Zhou Yuyan, Zhang Ailing, Gong Pifang, Qi Guibo, Song Xuan, Wang Zhenru, Shi Xuanming, Qi Congcong, Qin Song
Department of Neurology, Shanghai Pudong Hospital and Department of Histoembryology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
Department of Anatomy, School of Basic Medical Sciences, Bengbu Medical University, Bengbu, 233030, China.
Development. 2025 Oct 15;152(20). doi: 10.1242/dev.204718. Epub 2025 Aug 5.
The hippocampus, a brain region that is crucial for cognitive learning, memory and emotional regulation, undergoes its primary development during embryonic and early postnatal stages. Krüppel-like factor 7 (KLF7), a transcription factor associated with autism spectrum disorder and intellectual developmental disorders, plays a pivotal role in brain development. In this study, we investigated the role of KLF7 in hippocampal development using conditional knockout mice [Emx1-Cre;Klf7Flox(F)/F]. We found that KLF7 deletion in hippocampal progenitors resulted in significant hippocampal shrinkage, disrupting neurogenesis, neuronal differentiation and migration. KLF7 mutant mice exhibited abnormal neuronal projections, anxiety- and depression-like behaviors, and memory impairments. Transcriptomic profiling identified Draxin, a neural chemorepellent, as a key downstream target of KLF7. Remarkably, overexpression of Draxin rescued dentate gyrus granule cell migration defects in KLF7 mutant mice. These findings demonstrate that KLF7 is essential for proper hippocampal development and function, regulating neuronal migration through Draxin. This study provides mechanistic insights into the neurological deficits associated with KLF7 pathogenic variants and highlights potential therapeutic targets for neurodevelopmental disorders.
海马体是大脑中对认知学习、记忆和情绪调节至关重要的区域，在胚胎期和出生后早期经历主要发育过程。Krüppel样因子7（KLF7）是一种与自闭症谱系障碍和智力发育障碍相关的转录因子，在大脑发育中起关键作用。在本研究中，我们使用条件性敲除小鼠[Emx1-Cre;Klf7Flox(F)/F]研究了KLF7在海马体发育中的作用。我们发现海马体祖细胞中KLF7的缺失导致海马体显著萎缩，破坏神经发生、神经元分化和迁移。KLF7突变小鼠表现出异常的神经元投射、焦虑和抑郁样行为以及记忆障碍。转录组分析确定神经化学排斥分子Draxin是KLF7的关键下游靶点。值得注意的是，Draxin的过表达挽救了KLF7突变小鼠齿状回颗粒细胞迁移缺陷。这些发现表明，KLF7对海马体的正常发育和功能至关重要，通过Draxin调节神经元迁移。本研究为与KLF7致病变体相关的神经功能缺陷提供了机制性见解，并突出了神经发育障碍的潜在治疗靶点。
