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Updated: Jan 2, 2026
Murine Dermal Fibroblast Isolation by FACS
Published on: January 7, 2016
Mouse genetics identifies unique and overlapping functions of fibroblast growth factor receptors in keratinocytes
Michael Meyer1, Maya Ben-Yehuda Greenwald1, Theresa Rauschendorfer1
1Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Abstract:
Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double-knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor.
Insights
Fibroblast growth factor receptors (FGFRs) maintain skin health. FGFR1, FGFR2, and FGFR3 work together to preserve epidermal integrity and skin homeostasis, with FGFR2 being most crucial.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- Fibroblast growth factors (FGFs) are vital for tissue development and repair.
- Aberrant FGF signaling is implicated in numerous human diseases.
- The role of Fibroblast growth factor receptor 3 (FGFR3) in keratinocytes regarding skin homeostasis was previously unknown.
Purpose of the Study:
- To investigate the function of FGFR3 in mouse skin development, homeostasis, and repair.
- To determine the consequences of FGFR3 deficiency in the epidermis.
- To elucidate the interplay between FGFR1, FGFR2, and FGFR3 in maintaining epidermal barrier function.
Main Methods:
- Gene knockout mouse models were utilized to study FGFR function.
- Analysis of skin development, homeostasis, and wound repair in mice with varying FGFR deficiencies.
- Histological examination to assess epidermal integrity and fibroblast activation.
Main Results:
- FGFR3 is dispensable for normal mouse skin development, homeostasis, and wound repair.
- Loss of FGFR1 and FGFR2 in keratinocytes leads to epidermal barrier defects and inflammatory skin disease.
- Combined deficiency of FGFR1, FGFR2, and FGFR3 exacerbates epidermal barrier defects, fibroblast activation, and fibrosis, indicating functional redundancy.
Conclusions:
- FGFR1, FGFR2, and FGFR3 collaborate to maintain epidermal integrity and cutaneous homeostasis.
- FGFR2 plays a dominant role among the three receptors in preserving skin barrier function.
- FGFR3 exhibits functional redundancy with FGFR1 and FGFR2 in maintaining epidermal integrity.
