With the introduction of hair regeneration techniques using epidermal and dermal cells, hair follicle regeneration became much easier and faster. Current success has been dependent on the availability of cells from newborn or embryonic mice. We recently observed that the hair-inducing ability of newborn mouse dermal cells disappeared in the first few days of life and there was a drastic decrease of histidine decarboxylase (HDC) gene expression from postnatal day 0 (p0) to day 7 (p7).The aim of this study was to study the role of HDC in hair follicle induction.The mRNA levels of HDC in p0, p7 and p48 C57BL/6 mouse skin were checked with a real time reverse transcription polymerase chain reaction and immunohistochemistry. To test the effect of HDC, HDC expression in p0 mouse dermal cells was suppressed with small interfering RNA (siRNA) transfection. Mock treated and HDC siRNA treated cells were then injected with adult epidermal cells into nude mice skin. Three weeks later, the number, length and thickness of induced hairs were compared.Compared with p0, the mRNA level of HDC was much lower at p7 and p48. Immunohistochemical staining also revealed a marked decrease of HDC expression in p7 mice skin, compared with p0 skin. Hair patch assays showed that the HDC siRNA treated p0 dermal cells induced less hair follicle structures and shorter and thinner hair shafts than mock treated cells.HDC, whose expression is remarkably downregulated during the first few days after birth in dermal cells of mice, plays essential roles in the hair-inducing ability of newborn mouse dermal cells.