title: ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration.
abstract: Epimorphic regeneration is a unique and complex instance of postembryonic growth observed in certain metazoans that is usually triggered by severe injury [Akimenko et al., 2003; Alvarado and Tsonis, 2006; Brockes, 1997; Endo et al., 2004]. Cell division and migration are two fundamental biological processes required for supplying replacement cells during regeneration [Endo et al., 2004; Slack, 2007]. However, the connection between the early stimuli generated after injury and the signals regulating proliferation and migration during regeneration remain largely unknown. Here we show that the oncogenes ErbB2 and ErbB3, two members of the EGFR family, are essential for mounting a successful regeneration response in vertebrates. Importantly, amputation-induced progenitor proliferation and migration are significantly reduced upon genetic and/or chemical modulation of ErbB function. Moreover, we also found that NRG1 and PI3K functionally interact with ErbB2 and ErbB3 during regeneration and interfering with their function also abrogates the capacity of progenitor cells to regenerate lost structures upon amputation. Our findings suggest that ErbB, PI3K and NRG1 are components of a permissive switch for migration and proliferation continuously acting across the amputated fin from early stages of vertebrate regeneration onwards that regulate the expression of the transcription factors lef1 and msxB.
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Agustin
authors.initials: A
authors.lastname: Rojas-Muñoz
authors.forename: Shibani
authors.initials: S
authors.lastname: Rajadhyksha
authors.forename: Darren
authors.initials: D
authors.lastname: Gilmour
authors.forename: Frauke
authors.initials: F
authors.lastname: van Bebber
authors.forename: Christopher
authors.initials: C
authors.lastname: Antos
authors.forename: Concepción
authors.initials: C
authors.lastname: Rodríguez Esteban
authors.forename: Christiane
authors.initials: C
authors.lastname: Nüsslein-Volhard
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisúa Belmonte
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000235:genetics; D020890:Neuregulin-1 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D020893:Receptor, ErbB-3 / Q000502:physiology*; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014714:Vertebrates; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014157:Transcription Factors; D029961:Zebrafish Proteins; C507321:LEF1 protein, zebrafish; C460082:msx1b protein, zebrafish