Regeneration of breeding tubercles on zebrafish pectoral fins requires androgens and two waves of revascularization

Development. 2013 Nov;140(21):4323-34. doi: 10.1242/dev.095992. Epub 2013 Oct 2.


Sexually dimorphic breeding tubercles (BTs) are keratinized epidermal structures that form clusters on the dorsal surface of the anterior rays of zebrafish male pectoral fins. BTs appear during sexual maturation and are maintained through regular shedding and renewal of the keratinized surface. Following pectoral fin amputation, BT clusters regenerate after the initiation of revascularization, but concomitantly with a second wave of angiogenesis. This second wave of regeneration forms a web-like blood vessel network that penetrates the supportive epidermis of BTs. Upon analyzing the effects of sex steroids and their inhibitors, we show that androgens induce and estrogens inhibit BT cluster formation in intact and regenerating pectoral fins. Androgen-induced BT formation in females is accompanied by the formation of a male-like blood vessel network. Treatment of females with both androgens and an angiogenesis inhibitor results in the formation of undersized BT clusters when compared with females treated with androgens alone. Overall, the growth and regeneration of large BTs requires a hormonal stimulus and the presence of an additional blood vessel network that is naturally found in males.

Keywords: Blood vessels; Breeding tubercles; Fin regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism*
  • Animal Fins / blood supply
  • Animal Fins / metabolism
  • Animal Fins / physiology*
  • Animals
  • DNA Primers / genetics
  • Epidermal Cells
  • Female
  • Histocytochemistry
  • Keratinocytes / metabolism
  • Male
  • Microscopy, Fluorescence
  • Neovascularization, Physiologic / physiology*
  • Real-Time Polymerase Chain Reaction
  • Regeneration / physiology*
  • Sex Characteristics*
  • Zebrafish / physiology*


  • Androgens
  • DNA Primers