ArticleProceedings of the National Academy of Sciences of the United States of America2014
Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Update on neuroimaging phenotypes of mid-hindbrain malformations.Neuroradiology · 2015Pooled it
- PRDM13 is required for specification of PAX2 lineage inhibitory neurons in the developing cerebellum.Developmental biology · 2025Article
- Mapping the developmental profile of ventricular zone-derived neurons in the human cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Ptf1a expression is necessary for correct targeting of spiral ganglion neurons within the cochlear nuclei.Neuroscience letters · 2023Article
- Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His.IBRO neuroscience reports · 2022Review
- Recessive PRDM13 mutations cause fatal perinatal brainstem dysfunction with cerebellar hypoplasia and disrupt Purkinje cell differentiation.American journal of human genetics · 2022Article
- Integrated single-cell transcriptomic and epigenetic study of cell state transition and lineage commitment in embryonic mouse cerebellum.Science advances · 2022Article
- Cerebellar dysfunction and schizophrenia-like behavior in Ebp1-deficient mice.Molecular psychiatry · 2022Article
- Head transcriptome profiling of glossiphoniid leech (Open biology · 2022Article
- Cerebellar development after preterm birth.Frontiers in cell and developmental biology · 2022Review
- A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia.The Journal of clinical investigation · 2021Article
- Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells.Science (New York, N.Y.) · 2021Article
- Olig3 regulates early cerebellar development.eLife · 2021Article
- The Role of Neurod Genes in Brain Development, Function, and Disease.Frontiers in molecular neuroscience · 2021Article
- E3 Ubiquitin Ligase TRIP12: Regulation, Structure, and Physiopathological Functions.International journal of molecular sciences · 2020Review
- Positive autofeedback regulation ofGenes & development · 2020Article
- An Improved Method for Differentiating Mouse Embryonic Stem Cells into Cerebellar Purkinje Neurons.Cerebellum (London, England) · 2019Article
- Transcription factor Ptf1a in development, diseases and reprogramming.Cellular and molecular life sciences : CMLS · 2019Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Model organism studies have demonstrated that cell fate specification decisions play an important role in normal brain development. Their role in human neurodevelopmental disorders, however, is poorly understood, with very few examples described. The cerebellum is an excellent system to study mechanisms of cell fate specification. Although signals from the isthmic organizer are known to specify cerebellar territory along the anterior-posterior axis of the neural tube, the mechanisms establishing the cerebellar anlage along the dorsal-ventral axis are unknown. Here we show that the gene encoding pancreatic transcription factor PTF1A, which is inactivated in human patients with cerebellar agenesis, is required to segregate the cerebellum from more ventral extracerebellar fates. Using genetic fate mapping in mice, we show that in the absence of Ptf1a, cells originating in the cerebellar ventricular zone initiate a more ventral brainstem expression program, including LIM homeobox transcription factor 1 beta and T-cell leukemia homeobox 3. Misspecified cells exit the cerebellar anlage and contribute to the adjacent brainstem or die, leading to cerebellar agenesis in Ptf1a mutants. Our data identify Ptf1a as the first gene involved in the segregation of the cerebellum from the more ventral brainstem. Further, we propose that cerebellar agenesis represents a new, dorsal-to-ventral, cell fate misspecification phenotype in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.