Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis

Development. 2014 Jul;141(14):2885-94. doi: 10.1242/dev.099150.

Abstract

Apoptosis is an important mechanism for sculpting morphology. However, the molecular cascades that control apoptosis in developing limb buds remain largely unclear. Here, we show that MafB was specifically expressed in apoptotic regions of chick limb buds, and MafB/cFos heterodimers repressed apoptosis, whereas MafB/cJun heterodimers promoted apoptosis for sculpting the shape of the limbs. Chromatin immunoprecipitation sequencing in chick limb buds identified potential target genes and regulatory elements controlled by Maf and Jun. Functional analyses revealed that expression of p63 and p73, key components known to arrest the cell cycle, was directly activated by MafB and cJun. Our data suggest that dimeric combinations of MafB, cFos and cJun in developing chick limb buds control the number of apoptotic cells, and that MafB/cJun heterodimers lead to apoptosis via activation of p63 and p73.

Keywords: AP-1 transcription factor; Chick; Limb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Binding Sites
  • Bone Morphogenetic Proteins / metabolism
  • Cell Survival
  • Chick Embryo
  • Chickens
  • Down-Regulation / genetics
  • Extremities / embryology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Limb Buds / cytology
  • Limb Buds / embryology
  • Limb Buds / metabolism
  • Macrophages / metabolism
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / metabolism*
  • Models, Biological
  • Morphogenesis* / genetics
  • Protein Binding
  • Protein Multimerization*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Signal Transduction / genetics
  • Transcription Factor AP-1 / metabolism
  • Tretinoin / metabolism

Substances

  • Bone Morphogenetic Proteins
  • MafB Transcription Factor
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Tretinoin