A new role for neurotrophin-3: Involvement in the regulation of hair follicle regression (catagen)

Vladimir A. Botchkarev, Pia Welker, Kathryn M. Albers, Natalia V. Botchkareva, Martin Metz, Gary R. Lewin, Silvia Bulfone-Paus, Eva M.J. Peters, Gerd Lindner, Ralf Paus

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Nervous system and hair follicle epithelium share a common ectodermal origin, and some neurotrophins (NTs) can modulate keratinocyte proliferation and apoptosis. Therefore, it is reasonable to ask whether NTs are also involved in hair growth control. Here, we show that the expression of NT-3 and its high-affinity receptor, tyrosine kinase C, in the skin of C57BL/6 mice is strikingly hair cycle-dependent, with maximal transcript and protein expression seen during spontaneous hair follicle regression (catagen). During catagen, NT-3 and tyrosine kinase C are coexpressed by terminal deoxynucleotidyl transferase-mediated in situ nick end labeling-positive keratinocytes in the club hair and secondary germ. NT-3-overexpressing transgenic mice show precocious catagen development during the postnatal initiation of hair follicle cycling, whereas heterozygous NT-3 knockout (+/- ) mice display a significant catagen retardation. Finally, NT-3 stimulates catagen development in organ culture of normal C57BL/6 mouse skin. These observations suggest that the hair follicle is both a source and target of NT-3 and that NT-3/tyrosine kinase C signaling is functionally important in the control of hair follicle regression. Therefore, tyrosine kinase C agonists and antagonists deserve systematic exploration for the management of hair growth disorders that are related to premature (alopecia/effluvium) or retarded catagen (hirsutism/hypertrichosis).

Original languageEnglish (US)
Pages (from-to)785-799
Number of pages15
JournalAmerican Journal of Pathology
Issue number3
StatePublished - Sep 1998
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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