ArticleDevelopment (Cambridge, England)2016
ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- Folic Acid Metabolism and Its Impact on Neurogenesis: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Chronic AMPK inactivation slows SHH medulloblastoma progression by inhibiting mTORC1 signaling and depleting tumor stem cells.iScience · 2023Article
- Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.Hereditas · 2023Article
- PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth.Acta neuropathologica communications · 2023Article
- Dissociation of Cerebellar Granule Neuron Progenitors for Culture, FACS, Transcriptomics, and Molecular Biology.Methods in molecular biology (Clifton, N.J.) · 2023Article
- P53 independent pathogenic mechanisms contribute to BubR1 microcephaly.Frontiers in cell and developmental biology · 2023Article
- Processing Neonatal Mouse Brains for Immunohistochemical Analysis: As Required for Including Spindle Orientation Analysis and Analysis of DNA Damage and Apoptosis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Proliferation Analysis of Cerebellar Granule Neuron Progenitors for Microcephaly Research, Using Immunofluorescent Staining and Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Conventional and Spectral Karyotyping of Murine Cerebellar Granule Neuron Progenitors.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Chromosomal Instability Characterizes Pediatric Medulloblastoma but Is Not Tolerated in the Developing Cerebellum.International journal of molecular sciences · 2022Article
- Chromosomal instability in adult-type diffuse gliomas.Acta neuropathologica communications · 2022Review
- Ruxolitinib ameliorates progressive anemia and improves survival during episodes of emergency granulopoiesis in Fanconi CExperimental hematology · 2022Article
- Enhancing CDK4/6 inhibitor therapy for medulloblastoma using nanoparticle delivery and scRNA-seq-guided combination with sapanisertib.Science advances · 2022Article
- Medulloblastoma and the DNA Damage Response.Frontiers in oncology · 2022Review
- Oligodendrocytes depend on MCL-1 to prevent spontaneous apoptosis and white matter degeneration.Cell death & disease · 2021Article
- ATR regulates neuronal activity by modulating presynaptic firing.Nature communications · 2021Article
- Cryptic developmental events determine medulloblastoma radiosensitivity and cellular heterogeneity without altering transcriptomic profile.Communications biology · 2021Article
- Antiapoptotic Bcl-2 family proteins BCL-xL and MCL-1 integrate neural progenitor survival and proliferation during postnatal cerebellar neurogenesis.Cell death and differentiation · 2021Article
- Poly(2-oxazoline) nanoparticle delivery enhances the therapeutic potential of vismodegib for medulloblastoma by improving CNS pharmacokinetics and reducing systemic toxicity.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
- Progenitor death drives retinal dysplasia and neuronal degeneration in a mouse model of ATRIP-Seckel syndrome.Disease models & mechanisms · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report that ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis and cerebellar hypoplasia in mice. Co-deletions of either p53 or Bax and Bak prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. ATR-deficient CGNPs had impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to ATR-deficient proliferation was highly p53 dependent and markedly attenuated by p53 co-deletion. Acute ATR inhibition in vivo by nanoparticle-formulated VE-822 reproduced the developmental disruptions seen with Atr deletion. Genetic deletion of Atr blocked tumorigenesis in medulloblastoma-prone SmoM2 mice. Our data show that p53-driven apoptosis and cell cycle arrest - and, in the absence of p53, non-apoptotic cell death - redundantly limit growth in ATR-deficient progenitors. These mechanisms may be exploited for treatment of CGNP-derived medulloblastoma using ATR inhibition.
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Registered trials
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.