E2F1 and p53 are dispensable, whereas p21(Waf1/Cip1) cooperates with Rb to restrict endoreduplication and apoptosis during skeletal myogenesis

Dev Biol. 2000 Nov 1;227(1):8-41. doi: 10.1006/dbio.2000.9892.

Abstract

We describe temporal and genetic analyses of partially rescued Rb mutant fetuses, mgRb:Rb-/-, that survive to birth and reveal specific defects in skeletal muscle differentiation. We show that in the absence of Rb, these fetuses exhibit increased apoptosis, bona fide endoreduplication, and incomplete differentiation throughout terminal myogenesis. These defects were further augmented in composite mutant fetuses, mgRb:Rb-/-:p21-/-, lacking both Rb and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Although E2F1 and p53 mediate ectopic DNA synthesis and cell death in several tissues in Rb mutant embryos, both endoreduplication and apoptosis persisted in mgRb:Rb-/-:E2F1-/- and mgRb:Rb-/-:p53-/- compound mutant muscles. Thus, combined inactivation of Rb and p21(Waf1/Cip1) augments endoreduplication and apoptosis, whereas E2F1 and p53 are dispensable during aberrant myogenesis in Rb-deficient fetuses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bone Diseases, Developmental / genetics
  • Bone Diseases, Developmental / metabolism
  • Bone Diseases, Developmental / pathology
  • Carrier Proteins*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Cyclins / metabolism*
  • DNA Replication*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Embryonic and Fetal Development
  • Gene Deletion
  • Histocytochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / metabolism
  • Polyploidy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Retinoblastoma-Binding Protein 1
  • Signal Transduction
  • Transcription Factor DP1
  • Transcription Factors / physiology*
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Arid4a protein, mouse
  • Carrier Proteins
  • Cdkn1a protein, mouse
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, mouse
  • RNA, Messenger
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Protein p53