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 journalArticlepeer-review

140 Scopus citations


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
Issue number13
StatePublished - Jul 1 2002
Externally publishedYes


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

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


Dive into the research topics of 'Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development'. Together they form a unique fingerprint.

Cite this