IGF signaling between blastema and wound epidermis is required for fin regeneration

被引:116
作者
Chablais, Fabian [1 ]
Jazwinska, Anna [1 ]
机构
[1] Univ Fribourg, Dept Med, Unit Anat, CH-1700 Fribourg, Switzerland
来源
DEVELOPMENT | 2010年 / 137卷 / 06期
基金
瑞士国家科学基金会;
关键词
IGF; Zebrafish; Regeneration; Fin; Blastema; Wound epidermis; NEWT LIMB REGENERATION; APPENDAGE REGENERATION; EXPRESSION ANALYSIS; SONIC-HEDGEHOG; GROWTH-FACTORS; CAUDAL FIN; ZEBRAFISH; PATHWAYS; AXOLOTL; GENES;
D O I
10.1242/dev.043885
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
In mammals, the loss of a limb is irreversible. By contrast, urodele amphibians and teleost fish are capable of nearly perfect regeneration of lost appendages. This ability depends on direct interaction between the wound epithelium and mesenchymal progenitor cells of the blastema. It has been known for decades that contact between the wound epithelium and the underlying blastema is essential for successful regeneration. However, the underlying mechanisms are poorly understood. Here, we show that upon amputation the blastema induces expression of the ligand Igf2b, which then activates IGF signaling specifically in cells of the adjacent apical epithelium. Inhibition of IGF signaling by either morpholino antisense technology, or by specific chemical inhibitors of Igf1 receptor function NVP-AEW541 and NVP-ADW742, impairs fin regeneration. At the cellular level, this block in regeneration is reflected by a lack of the distinctive basal epithelium, increased apoptosis in the wound epidermis and reduced proliferation of blastema cells. Furthermore, induction of the blastemal and wound epidermal markers cannot be supported in the absence of IGF signaling. These data provide evidence that Igf2b expressed in the blastema promotes the properties of the adjacent wound epidermis, which subsequently are necessary for blastema function. Thus, IGF signaling upregulated upon fin amputation represents a signal from the blastema to the wound epithelium, a crucial step in appendage regeneration.
引用
收藏
页码:871 / 879
页数:9
相关论文
共 51 条
  • [41] Gene expression analysis on sections of zebrafish regenerating fins reveals limitations in the whole-mount in situ hybridization method
    Smith, A.
    Zhang, J.
    Guay, D.
    Quint, E.
    Johnson, A.
    Akimenko, M. A.
    [J]. DEVELOPMENTAL DYNAMICS, 2008, 237 (02) : 417 - 425
  • [42] Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine
    Stoick-Cooper, Cristi L.
    Moon, Randall T.
    Weidinger, Gilbert
    [J]. GENES & DEVELOPMENT, 2007, 21 (11) : 1292 - 1315
  • [43] Distinct Wnt signaling pathways have opposing roles in appendage regeneration
    Stoick-Cooper, Cristi L.
    Weidinger, Gilbert
    Riehle, Kimberly J.
    Hubbert, Charlotte
    Major, Michael B.
    Fausto, Nelson
    Moon, Randall T.
    [J]. DEVELOPMENT, 2007, 134 (03): : 479 - 489
  • [44] REGENERATIVE RESPONSES IN LARVAL AXOLOTL LIMBS WITH SKIN-GRAFTS OVER THE AMPUTATION SURFACE
    TASSAVA, RA
    GARLING, DJ
    [J]. JOURNAL OF EXPERIMENTAL ZOOLOGY, 1979, 208 (01): : 97 - +
  • [45] THE EFFECT OF APICAL CAP REMOVAL ON LIMB REGENERATION IN AMBLYSTOMA LARVAE
    THORNTON, CS
    [J]. JOURNAL OF EXPERIMENTAL ZOOLOGY, 1957, 134 (02): : 357 - 377
  • [46] Regulation of wound healing by growth factors and cytokines
    Werner, S
    Grose, R
    [J]. PHYSIOLOGICAL REVIEWS, 2003, 83 (03) : 835 - 870
  • [47] WHITE JA, 1994, DEVELOPMENT, V120, P1861
  • [48] fgf20 is essential for initiating zebrafish fin regeneration
    Whitehead, GG
    Makino, S
    Lien, CL
    Keating, MT
    [J]. SCIENCE, 2005, 310 (5756) : 1957 - 1960
  • [49] Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish
    Yin, Viravuth P.
    Thomson, J. Michael
    Thummel, Ryan
    Hyde, David R.
    Hammond, Scott M.
    Poss, Kenneth D.
    [J]. GENES & DEVELOPMENT, 2008, 22 (06) : 728 - 733