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c-Jun regulates eyelid closure and skin tumor development through EGFR signaling
Rainer Zenz1, Harald Scheuch, Paul Martin
1Research Institute of Molecular Pathology (IMP), A-1030, Vienna, Austria.
Abstract:
To investigate the function of c-Jun during skin development and skin tumor formation, we conditionally inactivated c-jun in the epidermis. Mice lacking c-jun in keratinocytes (c-jun(Deltaep)) develop normal skin but express reduced levels of EGFR in the eyelids, leading to open eyes at birth, as observed in EGFR null mice. Primary keratinocytes from c-jun(Deltaep) mice proliferate poorly, show increased differentiation, and form prominent cortical actin bundles, most likely because of decreased expression of EGFR and its ligand HB-EGF. In the absence of c-Jun, tumor-prone K5-SOS-F transgenic mice develop smaller papillomas, with reduced expression of EGFR in basal keratinocytes. Thus, using three experimental systems, we show that EGFR and HB-EGF are regulated by c-Jun, which controls eyelid development, keratinocyte proliferation, and skin tumor formation.
Insights
The transcription factor c-Jun regulates skin development and tumor formation by controlling epidermal growth factor receptor (EGFR) and HB-EGF expression. Its absence impacts eyelid opening, keratinocyte proliferation, and tumor growth.
Area of Science:
- Dermatology
- Molecular Biology
- Developmental Biology
Background:
- c-Jun is a transcription factor involved in various cellular processes.
- Its specific role in skin development and tumorigenesis requires further elucidation.
Purpose of the Study:
- To investigate the function of c-Jun in mouse skin development and tumor formation.
- To determine the regulatory role of c-Jun in EGFR and HB-EGF expression.
Main Methods:
- Conditional inactivation of c-jun in mouse epidermis (c-jun(Deltaep) mice).
- Analysis of skin and eyelid development in knockout mice.
- Assessment of primary keratinocyte proliferation and differentiation.
- Evaluation of skin tumor formation in K5-SOS-F transgenic mice lacking c-Jun.
Main Results:
- Mice lacking c-Jun in keratinocytes exhibit normal skin but reduced EGFR in eyelids, causing delayed eye opening.
- Primary keratinocytes from these mice show impaired proliferation, enhanced differentiation, and altered actin organization.
- Reduced expression of EGFR and HB-EGF was observed in c-jun deficient keratinocytes.
- In tumor-prone mice, absence of c-Jun led to smaller papillomas with decreased EGFR in basal keratinocytes.
Conclusions:
- c-Jun regulates eyelid development, keratinocyte proliferation, and skin tumor formation.
- EGFR and HB-EGF are key downstream targets regulated by c-Jun in the epidermis.
- These findings highlight c-Jun's critical role in skin homeostasis and oncogenesis.