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AP-2 factors act in concert with Notch to orchestrate terminal differentiation in skin epidermis

Xuan Wang1, H Amalia Pasolli, Trevor Williams

  • 1The Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.

The Journal of Cell Biology
|October 1, 2008
PubMed

Insights

Transcription factors AP-2alpha and AP-2gamma are essential for mammalian epidermal stem cell differentiation. Their deficiency disrupts terminal differentiation and hair follicle development, revealing parallel pathways with Notch signaling.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Mammalian epidermal stem cell differentiation mechanisms remain unclear.
  • Transcription factors AP-2alpha and AP-2gamma are highly expressed in the epidermis.

Purpose of the Study:

  • To investigate the role of AP-2alpha and AP-2gamma in epidermal stem cell differentiation.
  • To elucidate the molecular pathways governing the transition from proliferation to differentiation.

Main Methods:

  • Conditional ablation of AP-2alpha and AP-2gamma in vivo and in vitro.
  • Analysis of gene expression, transcription factors, and structural genes.
  • Dissection of molecular pathways involving AP-2 and Notch signaling.

Main Results:

  • AP-2 deficiency minimally affected basal gene expression but severely impaired terminal differentiation.
  • AP-2 and Notch signaling pathways converge on CCAAT/enhancer binding protein genes.
  • Compromised AP-2 or Notch signaling repressed hair follicle and sebaceous gland differentiation, leading to premalignant changes.

Conclusions:

  • AP-2 transcription factors are crucial for epidermal stem cell terminal differentiation.
  • Parallel AP-2 and Notch signaling pathways regulate epidermal differentiation.
  • Dysregulation of these pathways contributes to hair follicle and sebaceous gland defects and premalignant skin conditions.

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