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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月2日

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  • Amnah Al-Sayyar,
  • Laure Salvon,
  • Narjess Haidar,
  • Paul Schult,
  • Oussama Kassem,
  • Rejane Rua,
  • Audrey Romano

摘要

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.