Molecular aspects of control in epidermal differentiation

Area of Science:

• Cell biology
• Molecular biology
• Dermatology

Background:

• Mammalian epidermis comprises distinct cell layers: basal, spinous, granular, and cornified, representing stages of differentiation.
• DNA synthesis and mitosis are typically confined to the basal layer, with their inhibition being a key step in keratinization.
• Recent evidence shows RNA synthesis occurs in differentiated epidermal cells, unlike DNA synthesis.

Purpose of the Study:

• To investigate the molecular mechanisms controlling epidermal differentiation.
• To determine if the synthesis of a specific histidine-rich protein in granular cells is regulated at the translational or transcriptional level.
• To explore the role of gene regulation in epidermal pathologies.

Main Methods:

• Isolation of different epidermal cell populations.
• In vitro DNA synthesis assays using isolated nuclei.
• In vitro translation of messenger RNA (mRNA) from isolated cells.
• In vitro transcription of chromatin from isolated cells.

Main Results:

• Isolated differentiated nuclei showed inhibited DNA replication in situ, suggesting a cytoplasmic inhibitor.
• A histidine-rich protein is specifically synthesized in granular cells, forming keratohyalin granules.
• In vitro translation indicated that mRNA for this protein is present only in granular cells.
• In vitro transcription supported transcriptional control, with RNA ratios consistent with the predicted mRNA.

Conclusions:

• Epidermal differentiation is primarily controlled at the transcriptional level ('gene-readout').
• Regulation of gene expression, specifically for the histidine-rich protein, is crucial for normal epidermal differentiation.
• Understanding these molecular controls offers insights into epidermal pathologies.