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Early Cerebellar Development in Relation to the Trigeminal System

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Abstract

Despite the wealth of knowledge of adult cerebellar connectivity, little is known about the developmental mechanisms that underpin its development. Early connectivity is important because it is the foundation of the neural networks crucial for neuronal function and serves as a scaffold on which later tracts form. Conventionally, it is believed that afferents from the vestibular system are the first to invade the cerebellum, at embryonic days (E) 11–E12/13 in mice, where they target the new born Purkinje cells. However, we have demonstrated that pioneer axons that originate from the trigeminal ganglia are already present in the cerebellar primordium by E9, a stage at which afferents from the vestibular ganglia have not yet reached the brainstem, where they target neurons of the cerebellar nuclei. An early-born subset of cerebellar nuclei may be derived from the mesencephalon. These may be the target of the earliest pioneer axons. They form the early connectivity at the rostral end. This is consistent with the notion that the formation of the antero-posterior axis follows a rostro-caudal sequence. The finding that trigeminal ganglion-derived pioneer axons enter the cerebellar primordium before Purkinje cells are born and target the cerebellar nuclei, reveals a novel perspective on the development of early cerebellar connectivity.

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Funding

This study was supported by grants from the Natural Sciences and Engineering Research Council (HM: NSERC Discovery Grant # RGPIN-2018–06040), The Children’s Hospital Research Institute of Manitoba (HM: CHRIM Grant # 320035), and Research Manitoba Tri-Council Bridge Funding Program (HM: Grant # 47955).

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  1. Department of Human Anatomy and Cell Science, The Children’s Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Rm 129 BMSB, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada

    Maryam Rahimi-Balaei & Hassan Marzban

  2. Department of Cell Biology & Anatomy and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada

    Richard Hawkes

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  1. Maryam Rahimi-Balaei
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Correspondence to Hassan Marzban.

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Rahimi-Balaei, M., Marzban, H. & Hawkes, R. Early Cerebellar Development in Relation to the Trigeminal System. Cerebellum 21, 784–790 (2022). https://doi.org/10.1007/s12311-022-01388-2

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