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Updated: May 28, 2026

Direct Reprogramming of Mouse Fibroblasts into Melanocytes
Published on: August 27, 2021
FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription
1Department of Dermatology, Boston University School of Medicine, 609 Albany Street, Boston, MA 02118, USA.
Abstract:
PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation.
Insights
Basic fibroblast growth factor (FGF2) and signal transducer and activator of transcription 3 (STAT3) signaling regulate paired box 3 (PAX3) in pigment cells. This pathway influences melanocyte number and melanin synthesis, impacting skin pigmentation.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Paired box 3 (PAX3) is crucial for melanocyte development, regulating microphthalmia-associated transcription factor (MITF) transcription.
- The precise regulatory mechanisms of PAX3 activity in pigment cells are not fully understood.
Purpose of the Study:
- To investigate the role of FGF2-STAT3 signaling in regulating PAX3 transcriptional activity.
- To elucidate the in vivo function of PAX3 in melanocyte development and pigmentation.
Main Methods:
- Generation of a transgenic mouse model with PAX3 expression driven by the tyrosinase promoter.
- Analysis of skin pigmentation, melanocyte number, and melanin synthesis in the generated mouse model.
Main Results:
- FGF2-STAT3 signaling was identified as a regulator of PAX3 transcriptional activity in pigment cells.
- Transgenic mice exhibited hyperpigmentation in the epidermis, specifically in ears and tails.
- Increased melanocyte proliferation and enhanced melanin synthesis contributed to the observed hyperpigmentation.
Conclusions:
- A novel pathway linking FGF2-STAT3 signaling to increased PAX3 transcription in the melanocyte lineage was delineated.
- This pathway plays a significant role in regulating melanocyte numbers and melanin levels.
- The findings suggest a potential strategy for inducing pigmentation through modulation of this pathway.
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