PTB Deficiency Causes the Loss of Adherens Junctions in the Dorsal Telencephalon and Leads to Lethal Hydrocephalus
Abstract
Polypyrimidine tract-binding protein (PTB) is a well-characterized RNA-binding protein and known to be preferentially expressed in neural stem cells (NSCs) in the central nervous system; however, its role in NSCs in the developing brain remains unclear. To explore the role of PTB in embryonic NSCs in vivo, Nestin-Cre-mediated conditional Ptb knockout mice were generated for this study. In the mutant forebrain, despite the depletion of PTB protein, neither abnormal neurogenesis nor flagrant morphological abnormalities were observed at embryonic day 14.5 (E14.5). Nevertheless, by 10 weeks, nearly all mutant mice succumbed to hydrocephalus (HC), which was caused by a lack of the ependymal cell layer in the dorsal cortex. Upon further analysis, a gradual loss of adherens junctions (AJs) was observed in the ventricular zone (VZ) of the dorsal telencephalon in the mutant brains, beginning at E14.5. In the AJs-deficient VZ, impaired interkinetic nuclear migration and precocious differentiation of NSCs were observed after E14.5. These findings demonstrated that PTB depletion in the dorsal telencephalon is causally involved in the development of HC and that PTB is important for the maintenance of AJs in the NSCs of the dorsal telencephalon.
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Loss of ependymal cells in pan-neuronal Ptbp1 mutants is restricted to the dorsal telencephalon, indicating variable roles for PTBP1 across brain regions.
“The loss of ependymal cells is restricted to the dorsal telencephalon, indicating variable roles for PTBP1 across brain regions.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [24]
Mice with pan-neuronal loss of Ptbp1 have grossly normal brain morphology at an early age but show progressive loss of ependymal cells from the lateral ventricles with hydrocephaly and die by 10 weeks after birth.
“Mice with pan-neuronal loss of Ptbp1 have grossly normal brain morphology at an early age, but show a progressive loss of ependymal cells from the lateral ventricles with hydrocephaly and die by 10 weeks after birth24.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [24]
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- Authors
- Shibasaki, T., Tokunaga, A., Sakamoto, R., Sagara, H., Noguchi, S., Sasaoka, T., & Yoshida, N.
- Affiliations
- The University of Tokyo (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Meiji (Japan) (JP)
- Kitasato University (JP)
- Corresponding author
- Shibasaki, Takayuki
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-06-17
- Volume
- 23
- Issue
- 8
- Pages
- 1824-1835
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2141934077
- Cited by
- 60
- References
- 59
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 2
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22500384, 22500286, 23790218, 22500343)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- polypyrimidine tract-binding protein, PTB, RNA-binding proteins, neural stem cells, adherens junctions, hydrocephalus, dorsal telencephalon, ventricular zone, interkinetic nuclear migration, neural stem cell differentiation, conditional knockout mice, forebrain development
- MeSH terms
- Animals, Hydrocephalus, Mice, Inbred C57BL, Telencephalon, Mice, Knockout, Adherens Junctions, Polypyrimidine Tract-Binding Protein, Mice, Mice, 129 Strain, Neural Stem Cells
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