Wnt/β-catenin signaling defines organizing centers that orchestrate growth and differentiation of the regenerating zebrafish caudal fin.
Zebrafish regenerate their fins via the formation of a population of progenitor cells, the blastema. Wnt/β-catenin signaling is essential for blastemal cell proliferation and patterning of the overlying epidermis. Yet, we find that β-catenin signaling is neither active in the epidermis nor the majority of the proliferative blastemal cells. Rather, tissue-specific pathway interference indicates that Wnt signaling in the nonproliferative distal blastema is required for cell proliferation in the proximal blastema, and signaling in cells lining the osteoblasts directs osteoblast differentiation. Thus, Wnt signaling regulates epidermal patterning, blastemal cell proliferation, and osteoblast maturation indirectly via secondary signals. Gene expression profiling, chromatin immunoprecipitation, and functional rescue experiments suggest that Wnt/β-catenin signaling acts through Fgf and Bmp signaling to control epidermal patterning, whereas retinoic acid and Hedgehog signals mediate its effects on blastemal cell proliferation. We propose that Wnt signaling orchestrates fin regeneration by defining organizing centers that instruct cellular behaviors of adjacent tissues.
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Daniel
D
Wehner
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Wiebke
W
Cizelsky
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Mohankrishna Dalvoy
MD
Vasudevaro
Biotechnology Center, Technische Universität Dresden, Tatzberg 47-49, 01307 Dresden, Germany.
Günes
G
Ozhan
Biotechnology Center, Technische Universität Dresden, Tatzberg 47-49, 01307 Dresden, Germany.
Christa
C
Haase
Biotechnology Center, Technische Universität Dresden, Tatzberg 47-49, 01307 Dresden, Germany.
Birgit
B
Kagermeier-Schenk
Biotechnology Center, Technische Universität Dresden, Tatzberg 47-49, 01307 Dresden, Germany.
Alexander
A
Röder
Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
Richard I
RI
Dorsky
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.
Enrico
E
Moro
Department of Biology, University of Padova, 35121 Padova, Italy.
Francesco
F
Argenton
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Michael
M
Kühl
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: gilbert.weidinger@uni-ulm.de.
Gilbert
G
Weidinger
D058500:Animal Fins / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D053823:Hedgehog Proteins / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D012038:Regeneration / Q000235:genetics*; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D008024:Ligands; D029961:Zebrafish Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors