Ephrin-A3 not only increases the density of hair follicles but also accelerates anagen development in neonatal mice.

Background: Ephrins are cell-membrane-bound ligands for Eph receptor tyrosine kinases (Eph). Although ephrins are known to regulate a variety of developmental processes, little is known of their role in hair development. Previously, we studied the gene expression of dermal papilla cells from androgenetic alopecia and found that ephrin-A3 was significantly down-regulated.

Objective: To characterize the expression of ephrin-A3 in the hair cycle and evaluate the effect of ephrin-A3 on hair growth.

Methods: We investigated gene expression and protein expression of each ephrin-As and EphAs in the skin of neonatal mice through the first and second hair cycle using quantitative PCR and immunohistochemical analysis, respectively. We also injected ephrin-A3 protein into the skin of neonatal mice and demonstrated the effect of ephrin-A3 on hair follicle development.

Results: Expression of ephrin-A3 revealed a rapid increase at the beginning of the anagen phase, a peak during the mid-anagen, and a rapid fading during the telogen phase. In addition, we found ephrin-A3 protein was expressed in the developing hair follicles with a characteristic spatiotemporal localization. Furthermore, injection of ephrin-A3 into the skin of neonatal mice markedly accelerated the differentiation process of hair follicles. In addition, injection of ephrin-A3 unexpectedly increased the number of hair follicles.

Conclusion: These findings demonstrated that ephrin-A3 not only accelerates anagen development but also increases the density of hair follicles, and also suggested that an ephrin-A-EphA signal pathway is closely involved in hair follicle development.