ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration

Agustin Rojas-Muñoz, Shibani Rajadhyksha, Darren Gilmour, Frauke van Bebber, Christopher Antos, Concepción Rodríguez Esteban, Christiane Nüsslein-Volhard, Juan Carlos Izpisua Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)177-190
Number of pages14
JournalDevelopmental Biology
Volume327
Issue number1
DOIs
StatePublished - Mar 1 2009

Keywords

  • ErbB2/ErbB3
  • PI3K
  • Regeneration
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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