The meningeal–cerebellar axis: a new perspective on cerebellar development

The cerebellum is a highly organized brain structure best known for its roles in motor control and sensorimotor integration. While cerebellar development has traditionally been attributed to intrinsic genetic programs and local cell-cell interactions, emerging evidence indicates that extrinsic cues particularly signals from the meninges also play a critical role in shaping its maturation. Studies indicate that the meninges release cytokines, chemokines, and growth factors including CXCL12, IGF-1, IL-33, FGF2, TGF-β, and retinoic acid that influence granule cell precursor (GCPs) proliferation, Purkinje cell (PC) maturation, radial glia organization, and synaptic refinement. In addition, meningeal immune cells form a dynamic interface that potentially shapes neuronal positioning and cerebellar circuit formation. Disruption of these signals through genetic mutations, immune dysregulation, or environmental insults lead to impaired foliation, ectopic neuronal migration, and aberrant cerebellar architecture. This review focuses on in vivo findings supporting an emerging concept of the meningeal-cerebellar axis in development. Understanding cerebellar maturation within this broader context offers new perspectives on the origins of neurodevelopmental disorders and points toward novel avenues for therapeutic intervention.

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Publication Details

Journal
Cellular and Molecular Life Sciences
Published
2025-12-02
DOI
https://doi.org/10.1007/s00018-025-05897-1
Primary Topic
Vestibular and auditory disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

The meningeal–cerebellar axis: a new perspective on cerebellar development

Réjane Rua, Audrey Romano, O. Kassem, Amnah Al-Sayyar et al.
Cellular and Molecular Life Sciences
Vestibular and auditory disorders
article

The meningeal–cerebellar axis: a new perspective on cerebellar development

Réjane Rua, Audrey Romano, O. Kassem, Amnah Al-Sayyar, Narjess Haidar, Paul A Schult, Laure Salvon
article en

Abstract

The cerebellum is a highly organized brain structure best known for its roles in motor control and sensorimotor integration. While cerebellar development has traditionally been attributed to intrinsic genetic programs and local cell-cell interactions, emerging evidence indicates that extrinsic cues particularly signals from the meninges also play a critical role in shaping its maturation. Studies indicate that the meninges release cytokines, chemokines, and growth factors including CXCL12, IGF-1, IL-33, FGF2, TGF-β, and retinoic acid that influence granule cell precursor (GCPs) proliferation, Purkinje cell (PC) maturation, radial glia organization, and synaptic refinement. In addition, meningeal immune cells form a dynamic interface that potentially shapes neuronal positioning and cerebellar circuit formation. Disruption of these signals through genetic mutations, immune dysregulation, or environmental insults lead to impaired foliation, ectopic neuronal migration, and aberrant cerebellar architecture. This review focuses on in vivo findings supporting an emerging concept of the meningeal-cerebellar axis in development. Understanding cerebellar maturation within this broader context offers new perspectives on the origins of neurodevelopmental disorders and points toward novel avenues for therapeutic intervention.

Cellular and Molecular Life SciencesVol. 82(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Aix-Marseille Université (FR), Centre d’Immunologie de Marseille-Luminy (FR)
Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Kuwait Foundation for the Advancement of Sciences, Centre National de la Recherche Scientifique
Openalex Percentile: Top 56%
Vestibular and auditory disorders
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