Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19 Arf senescence pathways

Anna V. Molofsky, Shenghui He, Mohammad Bydon, Sean J. Morrison, Ricardo Pardal

Research output: Contribution to journalArticle

467 Citations (Scopus)

Abstract

Bmi-1 is required for the post-natal maintenance of stem cells in multiple tissues including the central nervous system (CNS) and peripheral nervous system (PNS). Deletion of Ink4a or Arf from Bmi-1-/- mice partially rescued stem cell self-renewal and stem cell frequency in the CNS and PNS, as well as forebrain proliferation and gut neurogenesis. Arf deficiency, but not Ink4a deficiency, partially rescued cerebellum development, demonstrating regional differences in the sensitivity of progenitors to p16Ink4a and p19Arf. Deletion of both Ink4a and Arf did not affect the growth or survival of Bmi-1-/- mice or completely rescue neural development. Bmi-1 thus prevents the premature senescence of neural stem cells by repressing Ink4a and Arf, but additional pathways must also function downstream of Bmi-1.

Original languageEnglish (US)
Pages (from-to)1432-1437
Number of pages6
JournalGenes and Development
Volume19
Issue number12
DOIs
StatePublished - Jun 15 2005
Externally publishedYes

Fingerprint

Neural Stem Cells
Peripheral Nervous System
Stem Cells
Central Nervous System
Neurogenesis
Growth
Prosencephalon
Cerebellum
Maintenance
Cell Self Renewal

Keywords

  • Bmi-1
  • Neural crest
  • p16
  • p19
  • Self-renewal
  • Stem cell

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19 Arf senescence pathways. / Molofsky, Anna V.; He, Shenghui; Bydon, Mohammad; Morrison, Sean J.; Pardal, Ricardo.

In: Genes and Development, Vol. 19, No. 12, 15.06.2005, p. 1432-1437.

Research output: Contribution to journalArticle

Molofsky, Anna V. ; He, Shenghui ; Bydon, Mohammad ; Morrison, Sean J. ; Pardal, Ricardo. / Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19 Arf senescence pathways. In: Genes and Development. 2005 ; Vol. 19, No. 12. pp. 1432-1437.
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