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microRNA-184 Induces a Commitment Switch to Epidermal Differentiation

Sara Nagosa1, Friederike Leesch1, Daria Putin1

  • 1Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.

Stem Cell Reports
|December 5, 2017
PubMed

Insights

MicroRNA-184 (miR-184) regulates skin cell differentiation by targeting K15 and FIH1. Mutations in miR-184 impair this process, leading to skin homeostasis issues.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • MicroRNA-184 (miRNA) is conserved across species, and its mutations are linked to blinding diseases.
  • The in vivo function of miR-184 in epidermal development and homeostasis remains largely unknown.

Purpose of the Study:

  • To investigate the role of miR-184 in epidermal development and differentiation.
  • To elucidate the molecular mechanisms by which miR-184 regulates epidermal homeostasis.

Main Methods:

  • Generation and analysis of a miR-184 knockout mouse model.
  • Forced expression of miR-184 in human epidermal stem/progenitor cells.
  • Analysis of gene expression, including p63, cytokeratin 15 (K15), and FIH1.
  • Investigation of the Notch signaling pathway activation.

Main Results:

  • miR-184 knockout mice exhibited increased p63 expression and epidermal hyperplasia.
  • Forced miR-184 expression enhanced Notch pathway signaling and induced epidermal hypoplasia.
  • miR-184 directly represses K15 and FIH1, promoting Notch activation and epidermal differentiation.
  • A disease-associated miR-184 mutant failed to repress K15 and FIH1, indicating a loss-of-function mechanism.

Conclusions:

  • miR-184 is a key regulator of epidermal homeostasis by controlling the transition from proliferation to differentiation.
  • Targeting K15 and FIH1 by miR-184 is crucial for Notch pathway activation and epidermal development.
  • Dysregulation or mutation of miR-184 can lead to impaired skin homeostasis and potentially disease.
Keywords:
FIH1K15corneaepidermishair folliclemiR-184miRNA-184microRNAnotchstem cells

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