A cell‐autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration
Open accessAbstract
Precise cell cycle regulation is critical for nervous system development. To assess the role of the cell cycle regulator, retinoblastoma (Rb) protein, in forebrain development, we studied mice with telencephalon-specific Rb deletions. We examined the role of Rb in neuronal specification and migration of diverse neuronal populations. Although layer specification occurred at the appropriate time in Rb mutants, migration of early-born cortical neurons was perturbed. Consistent with defects in radial migration, neuronal cell death in Rb mutants specifically affected Cajal-Retzius neurons. In the ventral telencephalon, although calbindin- and Lhx6-expressing cortical neurons were generated at embryonic day 12.5, their tangential migration into the neocortex was dramatically and specifically reduced in the mutant marginal zone. Cell transplantation assays revealed that defects in tangential migration arose owing to a cell-autonomous loss of Rb in migrating interneurons and not because of a defective cortical environment. These results revealed a cell-autonomous role for Rb in regulating the tangential migration of cortical interneurons. Taken together, we reveal a novel requirement for the cell cycle protein, Rb, in the regulation of neuronal migration.
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Loss of RB causes inappropriate neuronal migration in the developing mouse cortex, and this phenotype depends on E2F3 activity.
“Loss of RB has been shown to produce inappropriate migration of neurons in the developing mouse cortex141, a phenotype that is dependent on E2F3 activity69.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [141]
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Cellular mechanisms of tumour suppression by the retinoblastoma gene
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- Authors
- Ferguson, K. L., McClellan, K. A., Vanderluit, J. L., McIntosh, W. C., Schuurmans, C., Polleux, F., & Slack, R. S.
- Affiliations
- University of Ottawa (CA)
- University of Calgary (CA)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Slack, Ruth S
- Venue
- The EMBO Journal
- Published
- 2005-11-24
- Volume
- 24
- Issue
- 24
- Pages
- 4381-4391
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1356328
- OpenAlex
- W2104822129
- Cited by
- 65
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 2 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 5 · 2012: 7
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- retinoblastoma protein, neuronal migration, tangential migration, radial migration, cortical interneurons, cell cycle regulation, Cajal-Retzius neurons, telencephalon, forebrain development, cell-autonomous function, marginal zone, Lhx6, calbindin, cell death
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Cell Movement, Cell Survival, Embryo, Mammalian, Genotype, Immunohistochemistry, Models, Anatomic, Mutation, Nerve Tissue Proteins, Neurons, Retinoblastoma, Stem Cells, Telencephalon, Time Factors, Transcription Factors, Retinoblastoma Protein, Apoptosis, In Situ Hybridization, Homeodomain Proteins, Gene Expression Regulation, Developmental, Coculture Techniques, Cell Lineage, Body Patterning, Mice, LIM-Homeodomain Proteins, Calbindins, S100 Calcium Binding Protein G
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