EGFL6 expression in hair follicle central isthmus is dependent on the presence of terminal Schwann cells

Hair follicle central isthmus is surrounded by dense nerve endings and terminal Schwann cells (TSCs), forming a specialized sensory structure called lanceolate complexes. Extracellular matrix protein EGFL6 expressed from epidermis has been found closely associated with lanceolate complexes and important for proper alignment of nerve fibres and TSCs processes, and for proper response to light touch. However, how EGFL6 itself is specifically induced/deposited/maintained at the central isthmus remains to be elucidated. Previous reports and our results showed that nerve endings and TSCs docking at the central isthmus during hair follicle development occur before the specific depositing of EGFL6 protein. Furthermore, we found nude mice rarely maintain the lanceolate complex, and EGFL6 is lost in their aberrant hair follicle. Instead, reconstituted hair follicle in nude mice by stem cells chamber grafting assay expresses EGFL6 at the central isthmus area after hair follicle innervation. At last, long-term but not short-term cutaneous denervation leads to degeneration of TSCs and loss of EGFL6 expression. Together, our results demonstrate that EGFL6 expression in the central isthmus is dependent on the presence of TSCs, proposing that the interplay of epidermis and neuronal components is important for maintaining functional structure of lanceolate complexes.