title: Denervation impairs regeneration of amputated zebrafish fins.
abstract: BACKGROUND
  Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear.
  
  
  RESULTS
  We have used zebrafish as a model system to address the role of nerve fibres in fin regeneration. We have developed a protocol for pectoral fin denervation followed by amputation and analysed the regenerative process under this experimental conditions. Upon denervation fins were able to close the wound and form a wound epidermis, but could not establish a functional apical epithelial cap, with a posterior failure of blastema formation and outgrowth, and the accumulation of several defects. The expression patterns of genes known to be key players during fin regeneration were altered upon denervation, suggesting that nerves can contribute to the regulation of the Fgf, Wnt and Shh pathways during zebrafish fin regeneration.
  
  
  CONCLUSIONS
  Our results demonstrate that proper innervation of the zebrafish pectoral fin is essential for a successful regenerative process, and establish this organism as a useful model to understand the molecular and cellular mechanisms of nerve dependence, during vertebrate regeneration.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal. mariana.simoes@fcm.unl.pt.|CEDOC, Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Campo dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal. mariana.simoes@fcm.unl.pt.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Simões
authors.affiliation: CEDOC, Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Campo dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal. anabela.brito@fcm.unl.pt.|Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal. anabela.brito@fcm.unl.pt.
authors.forename: Anabela
authors.initials: A
authors.lastname: Bensimon-Brito
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal. mgf25@cam.ac.uk.
authors.forename: Mariana
authors.initials: M
authors.lastname: Fonseca
authors.affiliation: CEDOC, Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Campo dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal. ana.farinho@fcm.unl.pt.
authors.forename: Ana
authors.initials: A
authors.lastname: Farinho
authors.affiliation: CEDOC, Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Campo dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal. fabio.valerio@fcm.unl.pt.
authors.forename: Fábio
authors.initials: F
authors.lastname: Valério
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal. ssousa@technophage.pt.
authors.forename: Sara
authors.initials: S
authors.lastname: Sousa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal. nafonso@technophage.pt.
authors.forename: Nuno
authors.initials: N
authors.lastname: Afonso
authors.affiliation: Division of Biosciences, Institute of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK. anoop.kumar@ucl.ac.uk.
authors.forename: Anoop
authors.initials: A
authors.lastname: Kumar
authors.affiliation: CEDOC, Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Campo dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal. antonio.jacinto@fcm.unl.pt.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jacinto
mesh_terms: D058500:Animal Fins / Q000294:innervation / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D003714:Denervation; D005260:Female; D015870:Gene Expression; D008648:Mesoderm / Q000166:cytology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012038:Regeneration; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D029961:Zebrafish Proteins