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p63 in corneal and epidermal differentiation.

Flavia Novelli1, Carlo Ganini2, Gerry Melino1

  • 1Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.

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|April 17, 2022
PubMed
Summary

The transcription factor p63 is crucial for skin and ectodermal tissue development. Mutations in the TP63 gene cause Ectrodactyly Ectodermal Dysplasia Clefting (EEC) syndrome, leading to ocular surface issues, with new therapies emerging.

Keywords:
Ectodermal dysplasiaEpitheliaEyeKeratinocytesLimbal stem cellSkinp63

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Area of Science:

  • Developmental Biology
  • Genetics
  • Ophthalmology

Background:

  • The p63 transcription factor, a member of the p53 family, is essential for epidermal and ectodermal tissue differentiation.
  • Mutations in the TP63 gene are linked to rare genetic disorders known as ectodermal dysplasias, which affect skin structure and ocular surfaces.
  • Ectrodactyly Ectodermal Dysplasia Clefting (EEC) syndrome is a notable example, characterized by epidermal abnormalities and significant ocular surface disease.

Purpose of the Study:

  • To review the critical roles of p63 in keratinocyte and corneal epithelial differentiation.
  • To emphasize the function of the ΔNp63α isoform in regulating limbal and epithelial stem cell commitment.
  • To summarize ocular phenotypes in TP63-mutation related EEC syndrome and discuss therapeutic strategies for ocular manifestations.

Main Methods:

  • Literature review focusing on the function of p63 in epithelial differentiation.
  • Analysis of ocular phenotypes associated with TP63 mutations in EEC syndrome.
  • Compilation of current and emerging therapeutic approaches for ocular surface disease in EEC syndrome.

Main Results:

  • p63 acts as a master regulator for epidermal differentiation and ectodermal development.
  • The ΔNp63α isoform plays a key role in the commitment of limbal stem cells and other epithelial stem cells.
  • TP63 mutations lead to specific ocular phenotypes in EEC syndrome, impacting the ocular surface.

Conclusions:

  • p63 is fundamental for maintaining ocular surface integrity and epithelial stem cell function.
  • Understanding p63's role is vital for diagnosing and managing EEC syndrome and related disorders.
  • Targeted therapeutic strategies are being developed to address the ocular complications of TP63-related ectodermal dysplasias.