ArticleDevelopmental neuroscience2020
The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors.
Article in Developmental neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Protein phosphatase EYA1 regulates the dephosphorylation and turnover of BCL2L12 to promote glioma development.International journal of biological sciences · 2025Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma.Cancer research · 2024Article
- EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression.Neuro-oncology · 2023Article
- Dephosphorylation of Six2Y129 protects tyrosine hydroxylase-positive cells in SNpc by regulating TEA domain 1 expression.iScience · 2023Article
- Cerebellum lineage allocation, morphogenesis and repair: impact of interplay amongst cells.Development (Cambridge, England) · 2022Review
- The Symmetry of Neural Stem Cell and Progenitor Divisions in the Vertebrate Brain.Frontiers in cell and developmental biology · 2022Review
- The Eyes Absent proteins in development and in developmental disorders.Biochemical Society transactions · 2021Review
- The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases.International journal of molecular sciences · 2021Review
- Otic Neurogenesis inFrontiers in neuroanatomy · 2021Article
- The multi-functional eyes absent proteins.Critical reviews in biochemistry and molecular biology · 2020Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
During neural development, stem and precursor cells can divide either symmetrically or asymmetrically. The transition between symmetric and asymmetric cell divisions is a major determinant of precursor cell expansion and neural differentiation, but the underlying mechanisms that regulate this transition are not well understood. Here, we identify the Sonic hedgehog (Shh) pathway as a critical determinant regulating the mode of division of cerebellar granule cell precursors (GCPs). Using partial gain and loss of function mutations within the Shh pathway, we show that pathway activation determines spindle orientation of GCPs, and that mitotic spindle orientation correlates with the mode of division. Mechanistically, we show that the phosphatase Eya1 is essential for implementing Shh-dependent GCP spindle orientation. We identify atypical protein kinase C (aPKC) as a direct target of Eya1 activity and show that Eya1 dephosphorylates a critical threonine (T410) in the activation loop. Thus, Eya1 inactivates aPKC, resulting in reduced phosphorylation of Numb and other components that regulate the mode of division. This Eya1-dependent cascade is critical in linking spindle orientation, cell cycle exit and terminal differentiation. Together these findings demonstrate that a Shh-Eya1 regulatory axis selectively promotes symmetric cell divisions during cerebellar development by coordinating spindle orientation and cell fate determinants.
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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.