Mapping the developmental profile of ventricular zone–derived neurons in the human cerebellum

The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC differentiation occurs in the outer subventricular zone (SVZ), a region absent in the mouse cerebellum. Human PCs are generated during a compact two-week period before the onset of cerebral cortex histogenesis. A subset of human PCs retain proliferative marker expression weeks after leaving the VZ, another feature not observed in rodents. Human PC maturation is protracted with an extensive migration and reorganization throughout development with dendritic arborization developing in late gestation. We define a continuous transcriptional cascade of PC development from neuroepithelial cells to mature PCs. In contrast, while human interneuronal progenitors are born beginning in early fetal development, they exhibit an even more protracted differentiation across late gestation and into postnatal ages. These findings show dynamic developmental process for human cerebellar GABAergic neurons and underscore the importance of the embryonic environment, with early disruptions having potentially significant impacts.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-04-18
DOI
https://doi.org/10.1073/pnas.2415425122
Citations
6
Primary Topic
Neurogenesis and neuroplasticity mechanisms
Type
article
Field-Weighted Citation Impact
7.91

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article

Mapping the developmental profile of ventricular zone–derived neurons in the human cerebellum

Joseph Golser, Guanyi He, Haodan Tan, Kimberly A. Aldinger et al.
6 citations
Proceedings of the National Academy of Sciences
Neurogenesis and neuroplasticity mechanisms
7.91
article

Mapping the developmental profile of ventricular zone–derived neurons in the human cerebellum

Joseph Golser, Guanyi He, Haodan Tan, Kimberly A. Aldinger, Kathleen Bach, Fabien Guimiot, Kathleen J. Millen, Jake Millman, Giulia Petrilli, Anusha Mishra, Férechté Encha‐Razavi, Evelina Silvestri, Parthiv Haldipur, Željka Krsnik, Liam D. Hendrikse, Anders W. Erickson, Zachary Thomson, Omar Khan, Janja Kopić, Michael D. Taylor
article en
6 citations

Abstract

The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC differentiation occurs in the outer subventricular zone (SVZ), a region absent in the mouse cerebellum. Human PCs are generated during a compact two-week period before the onset of cerebral cortex histogenesis. A subset of human PCs retain proliferative marker expression weeks after leaving the VZ, another feature not observed in rodents. Human PC maturation is protracted with an extensive migration and reorganization throughout development with dendritic arborization developing in late gestation. We define a continuous transcriptional cascade of PC development from neuroepithelial cells to mature PCs. In contrast, while human interneuronal progenitors are born beginning in early fetal development, they exhibit an even more protracted differentiation across late gestation and into postnatal ages. These findings show dynamic developmental process for human cerebellar GABAergic neurons and underscore the importance of the embryonic environment, with early disruptions having potentially significant impacts.

Proceedings of the National Academy of SciencesVol. 122(17)
Hôpital Necker-Enfants Malades (FR), Inserm (FR), University of Zagreb (HR), Baylor College of Medicine (US), University of Toronto (CA), University of Washington (US), Hospital for Sick Children (CA), Assistance Publique – Hôpitaux de Paris (FR), Brain Tumour Research (GB), Hôpital Robert-Debré (FR), Nini Hospital (LB), Texas Children's Hospital (US), Children's Cancer Center (US), Biologie du Développement et Cellules Souches (FR), Benaroya Research Institute
Brain and Behavior Research Foundation, National Institute of Neurological Disorders and Stroke
Life in Land
Openalex Percentile: Top 3%
Neurogenesis and neuroplasticity mechanisms
7.91
DOIOpen Access PDFOpenAlex
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