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 Izpisúa Belmonte

doi:10.1016/j.ydbio.2008.12.012

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 Izpisúa Belmonte^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

55 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 language	English (US)
Pages (from-to)	177-190
Number of pages	14
Journal	Developmental Biology
Volume	327
Issue number	1
DOIs	https://doi.org/10.1016/j.ydbio.2008.12.012
State	Published - Mar 1 2009
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to Hans-Martin Maischein and Judith Konantz for technical assistance, to Yasuhiko Kawakami and Fernando Lopez-Casillas for critical reading of the manuscript and William Alaynick for building the tweezer electrodes. We thank Jörg Odenthal and Hinrich Habeck for identifying the allele hps t20458 , Robert Geisler for help with mutant cloning and Madeleine van Drenth for the NBT:DsR2 line. Many of the mutants described here were isolated during the Tübingen 2000 screen and we would like to acknowledge the contribution made by members of the Tübingen 2000 screen consortium (names listed in Supporting Online Material). Work in the laboratory of J.C.I.B. was funded by grants from the MEC, Marato, G. Harold and Leila Y. Mathers Charitable Foundation and Fundacion Cellex.

Keywords

ErbB2/ErbB3
PI3K
Regeneration
Zebrafish

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.ydbio.2008.12.012

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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.",

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author = "Agustin Rojas-Mu{\~n}oz and Shibani Rajadhyksha and Darren Gilmour and {van Bebber}, Frauke and Christopher Antos and {Rodr{\'i}guez Esteban}, Concepci{\'o}n and Christiane N{\"u}sslein-Volhard and {Izpis{\'u}a Belmonte}, {Juan Carlos}",

note = "Funding Information: We are grateful to Hans-Martin Maischein and Judith Konantz for technical assistance, to Yasuhiko Kawakami and Fernando Lopez-Casillas for critical reading of the manuscript and William Alaynick for building the tweezer electrodes. We thank J{\"o}rg Odenthal and Hinrich Habeck for identifying the allele hps t20458 , Robert Geisler for help with mutant cloning and Madeleine van Drenth for the NBT:DsR2 line. Many of the mutants described here were isolated during the T{\"u}bingen 2000 screen and we would like to acknowledge the contribution made by members of the T{\"u}bingen 2000 screen consortium (names listed in Supporting Online Material). Work in the laboratory of J.C.I.B. was funded by grants from the MEC, Marato, G. Harold and Leila Y. Mathers Charitable Foundation and Fundacion Cellex. ",

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AU - Rojas-Muñoz, Agustin

AU - Rajadhyksha, Shibani

AU - Gilmour, Darren

AU - van Bebber, Frauke

AU - Antos, Christopher

AU - Rodríguez Esteban, Concepción

AU - Nüsslein-Volhard, Christiane

AU - Izpisúa Belmonte, Juan Carlos

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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