ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 114 citations in OpenAlex.
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- Arrested development: the dysfunctional life history of medulloblastoma.Genes & development · 2025Review
- TLX3 regulates CGN progenitor proliferation during cerebellum development and its dysfunction can lead to autism.iScience · 2024Article
- Cerebellum Lecture: the Cerebellar Nuclei-Core of the Cerebellum.Cerebellum (London, England) · 2024Review
- Foxp and Skor family proteins control differentiation of Purkinje cells from Ptf1a- and Neurog1-expressing progenitors in zebrafish.Development (Cambridge, England) · 2024Article
- Ptf1a expression is necessary for correct targeting of spiral ganglion neurons within the cochlear nuclei.Neuroscience letters · 2023Article
- Early Cerebellar Development in Relation to the Trigeminal System.Cerebellum (London, England) · 2022Review
- Cerebellum lineage allocation, morphogenesis and repair: impact of interplay amongst cells.Development (Cambridge, England) · 2022Review
- Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases.Scientific reports · 2022Article
- M2 microglia-derived extracellular vesicles promote white matter repair and functional recovery via miR-23a-5p after cerebral ischemia in mice.Theranostics · 2022Article
- Neurosensory development of the four brainstem-projecting sensory systems and their integration in the telencephalon.Frontiers in neural circuits · 2022Article
- Cerebellar development after preterm birth.Frontiers in cell and developmental biology · 2022Review
- Transcriptome programs involved in the development and structure of the cerebellum.Cellular and molecular life sciences : CMLS · 2021Review
- The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum.Cell death and differentiation · 2021Article
- Diagnostic Approach to Cerebellar Hypoplasia.Cerebellum (London, England) · 2021Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the cerebellum, the bHLH transcription factors Ptf1a and Atoh1 are expressed in distinct neuroepithelial regions, the ventricular zone (VZ) and the rhombic lip (RL), and are required for producing GABAergic and glutamatergic neurons, respectively. However, it is unclear whether Ptf1a or Atoh1 is sufficient for specifying GABAergic or glutamatergic neuronal fates. To test this, we generated two novel knock-in mouse lines, Ptf1a(Atoh1) and Atoh1(Ptf1a), that are designed to express Atoh1 and Ptf1a ectopically in the VZ and RL, respectively. In Ptf1a(Atoh1) embryos, ectopically Atoh1-expressing VZ cells produced glutamatergic neurons, including granule cells and deep cerebellar nuclei neurons. Correspondingly, in Atoh1(Ptf1a) animals, ectopically Ptf1a-expressing RL cells produced GABAergic populations, such as Purkinje cells and GABAergic interneurons. Consistent results were also obtained from in utero electroporation of Ptf1a or Atoh1 into embryonic cerebella, suggesting that Ptf1a and Atoh1 are essential and sufficient for GABAergic versus glutamatergic specification in the neuroepithelium. Furthermore, birthdating analyses with BrdU in the knock-in mice or with electroporation studies showed that ectopically produced fate-changed neuronal types were generated at temporal schedules closely simulating those of the wild-type RL and VZ, suggesting that the VZ and RL share common temporal information. Observations of knock-in brains as well as electroporated brains revealed that Ptf1a and Atoh1 mutually negatively regulate their expression, probably contributing to formation of non-overlapping neuroepithelial domains. These findings suggest that Ptf1a and Atoh1 specify spatial identities of cerebellar neuron progenitors in the neuroepithelium, leading to appropriate production of GABAergic and glutamatergic neurons, respectively.
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