Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development

Kerry L. Ferguson, Jacqueline L. Vanderluit, Jean M. Hébert, W. C. McIntosh, Emma Tibbo, Jason G. MacLaurin, David S. Park, Valerie A. Wallace, Marc Vooijs, Susan K. McConnell, Ruth S. Slack

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

Correct cell cycle regulation and terminal mitosis are critical for nervous system development. The retinoblastoma (Rb) protein is a key regulator of these processes, as Rb-/- embryos die by E15.5, exhibiting gross hematopoietic and neurological defects. The extensive apoptosis in Rb-/- embryos has been attributed to aberrant S phase entry resulting in conflicting growth control signals in differentiating cells. To assess the role of Rb in cortical development in the absence of other embryonic defects, we examined mice with telencephalon-specific Rb deletions. Animals carrying a floxed Rb allele were interbred with mice in which cre was knocked into the Foxg1 locus. Unlike germline knockouts, mice specifically deleted for Rb in the developing telencephalon survived until birth. In these mutants, Rb-/- progenitor cells divided ectopically, but were able to survive and differentiate. Mutant brains exhibited enhanced cellularity due to increased proliferation of neuroblasts. These studies demonstrate that: (i) cell cycle deregulation during differentiation does not necessitate apoptosis; (ii) Rbdeficient mutants exhibit enhanced neuroblast proliferation; and (iii) terminal mitosis may not be required to initiate differentiation.

Original languageEnglish (US)
Pages (from-to)3337-3346
Number of pages10
JournalEMBO Journal
Volume21
Issue number13
DOIs
StatePublished - Jul 1 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Cell cycle
  • Central nervous system
  • Differentiation
  • Retinoblastoma

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Ferguson, K. L., Vanderluit, J. L., Hébert, J. M., McIntosh, W. C., Tibbo, E., MacLaurin, J. G., Park, D. S., Wallace, V. A., Vooijs, M., McConnell, S. K., & Slack, R. S. (2002). Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. EMBO Journal, 21(13), 3337-3346. https://doi.org/10.1093/emboj/cdf338