Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality.
Open accessAbstract
The adult mammalian cortex is characterized by a distinct laminar structure generated through a well-defined pattern of neuronal migration. Successively generated neurons are layered in an "inside-out" manner to produce six cortical laminae. We demonstrate here that p35, the neuronal-specific activator of cyclin-dependent kinase 5, plays a key role in proper neuronal migration. Mice lacking p35, and thus p35/cdk5 kinase activity, display severe cortical lamination defects and suffer from sporadic adult lethality and seizures. Histological examination reveals that the mutant mice lack the characteristic laminated structure of the cortex. Neuronal birth-dating experiments indicate a reversed packing order of cortical neurons such that earlier born neurons reside in superficial layers and later generated neurons occupy deep layers. The phenotype of p35 mutant mice thus demonstrates that the formation of cortical laminar structure depends on the action of the p35/cdk5 kinase.
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Genetic ablation of the CDK5 activator p35 increases susceptibility to spontaneous seizures in mice.
“For instance, genetic ablation of the CDK5 activator, p35, increases susceptibility to spontaneous seizures in mice (Chae et al., 1997).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Chae et al., 1997
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“For instance, genetic ablation of the CDK5 activator, p35, increases susceptibility to spontaneous seizures in mice (Chae et al., 1997).”
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- Authors
- Chae, T., Kwon, Y. T., Bronson, R., Dikkes, P., Li, E., & Tsai, L.-H.
- Affiliations
- Harvard University (US)
- Tufts University (US)
- Boston Children's Hospital (US)
- Corresponding author
- Tsai, Li-Huei
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1997-01
- Volume
- 18
- Issue
- 1
- Pages
- 29-42
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2038901745
- Cited by
- 715
- References
- 4
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 15 · 2021: 8 · 2020: 12 · 2019: 10 · 2018: 11 · 2017: 16 · 2016: 10 · 2015: 16 · 2014: 16 · 2013: 19 · 2012: 24
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM053049, GM52106, GM53049, R01GM052106)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- p35, cyclin-dependent kinase 5, cortical lamination, neuronal migration, seizures
- MeSH terms
- Animals, Cerebral Cortex, Crosses, Genetic, Embryonic and Fetal Development, Humans, Mice, Neurologic Mutants, Neurons, Recombination, Genetic, Seizures, Genomic Library, Polymerase Chain Reaction, Open Reading Frames, Protein Serine-Threonine Kinases, Gene Deletion, Mice, Knockout, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase 5, Mice
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