ZFIN ID: ZDB-PUB-100525-5
Ras controls melanocyte expansion during zebrafish fin stripe regeneration
Lee, Y., Nachtrab, G., Klinsawat, P.W., Hami, D., and Poss, K.D.
Date: 2010
Source: Disease models & mechanisms   3(7-8): 496-503 (Journal)
Registered Authors: Lee, Yoonsung, Nachtrab, Greg, Poss, Kenneth D.
Keywords: none
MeSH Terms:
  • Animal Structures/cytology*
  • Animal Structures/metabolism
  • Animal Structures/physiology*
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Proliferation
  • Melanocytes/cytology*
  • Melanocytes/metabolism
  • Pigmentation/physiology
  • Regeneration/physiology*
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
  • ras Proteins/metabolism*
PubMed: 20483996 Full text @ Dis. Model. Mech.
Regenerative medicine for complex tissues like limbs will require the provision or activation of precursors for different cell types, in the correct number, and with the appropriate instructions. These strategies can be guided by what is learned from spectacular events of natural limb or fin regeneration in urodele amphibians and teleost fish. Following zebrafish fin amputation, melanocyte stripes faithfully regenerate in tandem with complex fin structures. Distinct populations of melanocyte precursors emerge and differentiate to pigment regenerating fins, yet the regulation of their proliferation and patterning is incompletely understood. Here, we found that transgenic increases in active Ras dose-dependently hyperpigmented regenerating zebrafish fins. Lineage tracing and marker analysis indicated that increases in active Ras stimulated the in situ amplification of undifferentiated melanocyte precursors expressing mitfa and kita. Active Ras also hyperpigmented early fin regenerates of kita mutants, which are normally devoid of primary regeneration melanocytes, suppressing defects in precursor function and survival. By contrast, this protocol had no noticeable impact on pigmentation by secondary regulatory melanocyte precursors in late-stage kita regenerates. Our results provide evidence that Ras activity levels control the repopulation and expansion of adult melanocyte precursors after tissue loss, enabling the recovery of patterned melanocyte stripes during zebrafish appendage regeneration.