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

Kerry L. Ferguson, Jacqueline L. Vanderluit, Jean M. Hebert, 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

125 Citations (Scopus)

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

Fingerprint

Telencephalon
Retinoblastoma
Neurogenesis
Cells
Apoptosis
Retinoblastoma Protein
Defects
Deregulation
Neurology
Brain
Animals
Mitosis
Cell Cycle
Embryonic Structures
S Phase
Knockout Mice
Nervous System
Stem Cells
Alleles
Parturition

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Ferguson, K. L., Vanderluit, J. L., Hebert, J. M., McIntosh, W. C., Tibbo, E., MacLaurin, J. G., ... 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

Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. / Ferguson, Kerry L.; Vanderluit, Jacqueline L.; Hebert, Jean M.; McIntosh, W. C.; Tibbo, Emma; MacLaurin, Jason G.; Park, David S.; Wallace, Valerie A.; Vooijs, Marc; McConnell, Susan K.; Slack, Ruth S.

In: EMBO Journal, Vol. 21, No. 13, 01.07.2002, p. 3337-3346.

Research output: Contribution to journalArticle

Ferguson, KL, Vanderluit, JL, Hebert, JM, McIntosh, WC, Tibbo, E, MacLaurin, JG, Park, DS, Wallace, VA, Vooijs, M, McConnell, SK & Slack, RS 2002, 'Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development', EMBO Journal, vol. 21, no. 13, pp. 3337-3346. https://doi.org/10.1093/emboj/cdf338
Ferguson, Kerry L. ; Vanderluit, Jacqueline L. ; Hebert, Jean M. ; McIntosh, W. C. ; Tibbo, Emma ; MacLaurin, Jason G. ; Park, David S. ; Wallace, Valerie A. ; Vooijs, Marc ; McConnell, Susan K. ; Slack, Ruth S. / Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. In: EMBO Journal. 2002 ; Vol. 21, No. 13. pp. 3337-3346.
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