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Generation and Culturing of Primary Human Keratinocytes from Adult Skin
10:42

Generation and Culturing of Primary Human Keratinocytes from Adult Skin

Published on: December 22, 2017

Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control

Cristina Mammucari1, Alice Tommasi di Vignano, Andrey A Sharov

  • 1Department of Biochemistry, Lausanne University, Epalinges, Switzerland.

Developmental Cell
|May 4, 2005
PubMed

Insights

Notch 1 signaling controls keratinocyte differentiation via direct p21 gene targeting and a Calcineurin-dependent pathway. This interaction impacts hair follicle development, highlighting a key link between these cellular pathways.

Area of Science:

  • Cell Biology
  • Dermatology
  • Molecular Biology

Background:

  • Notch and Calcineurin/NFAT pathways regulate keratinocyte differentiation.
  • Notch 1 activation influences p21(WAF1/Cip1) gene expression via RBP-Jkappa.
  • The precise mechanisms linking these pathways in keratinocytes require further elucidation.

Purpose of the Study:

  • To investigate the role of Calcineurin in Notch 1-mediated keratinocyte differentiation.
  • To elucidate the molecular mechanisms underlying the interplay between Notch 1 and Calcineurin/NFAT signaling.
  • To determine the in vivo relevance of this interaction in skin homeostasis and hair follicle biology.

Main Methods:

  • Analysis of p21 promoter activity in response to Notch 1 activation.
  • Investigation of Calcineurin/NFAT pathway modulation by Notch signaling.
  • Assessment of Calcipressin and HES-1 expression.
  • Phenotypic analysis of Calcineurin B1 gene-deleted mice skin.

Main Results:

  • Notch 1 activation impacts p21 expression through both RBP-Jkappa-dependent and Calcineurin-dependent mechanisms.
  • Notch signaling enhances Calcineurin/NFAT activity by downregulating Calcipressin via HES-1.
  • Calcineurin is crucial for the broader transcriptional response to Notch 1 in keratinocytes.
  • Calcineurin B1 deficiency in skin leads to alopecia and altered expression of Notch-responsive genes.

Conclusions:

  • A significant functional interconnection exists between Notch 1 and Calcineurin-NFAT pathways in keratinocyte growth and differentiation.
  • This interplay is critical for maintaining skin homeostasis and hair follicle structure.
  • Targeting these pathways could offer therapeutic strategies for skin disorders.

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