{"title":"KLF7 orchestrates hippocampal development through neurogenesis and Draxin-mediated neuronal migration.","authors":"Yitong Liu, Wentong Hong, Yuyan Zhou, Ailing Zhang, Pifang Gong, Guibo Qi, Xuan Song, Zhenru Wang, Xuanming Shi, Congcong Qi, Song Qin","doi":"10.1242/dev.204718","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377812/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/dev.204718","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
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To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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