Arhgef7 is essential for granule cell precursor proliferation and migration during cerebellum development

During cerebellar development, granule cell precursors (GCPs) undergo a series of tightly regulated events, including proliferation, migration, and differentiation. Arhgef7, a guanine nucleotide exchange factor for Rac1 and Cdc42, plays a crucial role in these processes. This study investigates the role of Arhgef7 in cerebellar development using conditional knockout (cKO) mice. We demonstrate that Arhgef7 is expressed in GCPs. Loss of <i>Arhgef7</i> in GCPs results in severe cerebellar hypoplasia and foliation defects, particularly affecting lobules VI/VII. <i>Arhgef7</i> cKO mice exhibit reduced postnatal GCP proliferation, disorganized cell layers, delayed differentiation, and impaired tangential and radial migration of GCPs. Our findings highlight the essential role of Arhgef7 in regulating multiple aspects of GCP development, thereby ensuring proper cerebellar morphogenesis.

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Publication Details

Journal
iScience
Published
2025-12-31
DOI
https://doi.org/10.1016/j.isci.2025.114580
Primary Topic
Neurogenesis and neuroplasticity mechanisms
Type
article
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article

Arhgef7 is essential for granule cell precursor proliferation and migration during cerebellum development

Patricia T. Yam, Nursen Balekoglu, Frédéric Charron, Vanesa Jiménez-Amilburu et al.
iScience
Neurogenesis and neuroplasticity mechanisms
article

Arhgef7 is essential for granule cell precursor proliferation and migration during cerebellum development

Patricia T. Yam, Nursen Balekoglu, Frédéric Charron, Vanesa Jiménez-Amilburu, Hugo Ducuing, Sneha Sukumaran
article en

Abstract

During cerebellar development, granule cell precursors (GCPs) undergo a series of tightly regulated events, including proliferation, migration, and differentiation. Arhgef7, a guanine nucleotide exchange factor for Rac1 and Cdc42, plays a crucial role in these processes. This study investigates the role of Arhgef7 in cerebellar development using conditional knockout (cKO) mice. We demonstrate that Arhgef7 is expressed in GCPs. Loss of <i>Arhgef7</i> in GCPs results in severe cerebellar hypoplasia and foliation defects, particularly affecting lobules VI/VII. <i>Arhgef7</i> cKO mice exhibit reduced postnatal GCP proliferation, disorganized cell layers, delayed differentiation, and impaired tangential and radial migration of GCPs. Our findings highlight the essential role of Arhgef7 in regulating multiple aspects of GCP development, thereby ensuring proper cerebellar morphogenesis.

iScienceVol. 29(2)
Montreal Clinical Research Institute (CA), McGill University (CA), Université de Montréal (CA)
Openalex Percentile: Top 28%
Neurogenesis and neuroplasticity mechanisms
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