FGFR4 signaling is a necessary step in limb muscle differentiation

Irene Marics, Francoise Padilla, Jean-Francois Guillemot, Martin Scaal, Christophe Marcelle

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In chick embryos, most if not all, replicating myoblasts present within the skeletal muscle masses express high levels of the FGF receptor FREK/FGFR4, suggesting an important role for this molecule during myogenesis. We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles. All muscle markers analyzed (such as Myf5, MyoD and the embryonic myosin heavy chain) are affected. We show that inhibition of FGFR4 signal results in an arrest of muscle progenitor differentiation, which can be rapidly reverted by the addition of exogenous FGF, rather than a modification in their proliferative capacities. Conversely, over-expression of FGF8 in somites promotes FGFR4 expression and muscle differentiation in this tissue. Together, these results demonstrate that in vivo, myogenic differentiation is positively controlled by FGF signaling, a notion that contrasts with the general view that FGF promotes myoblast proliferation and represses myogenic differentiation. Our data assign a novel role to FGF8 during chick myogenesis and demonstrate that FGFR4 signaling is a crucial step in the cascade of molecular events leading to terminal muscle differentiation.
Original languageEnglish
Pages (from-to)4559 - 4569
Number of pages11
JournalDevelopment
Volume129
Issue number19
Publication statusPublished - 2002

Cite this

Marics, I., Padilla, F., Guillemot, J-F., Scaal, M., & Marcelle, C. (2002). FGFR4 signaling is a necessary step in limb muscle differentiation. Development, 129(19), 4559 - 4569.
Marics, Irene ; Padilla, Francoise ; Guillemot, Jean-Francois ; Scaal, Martin ; Marcelle, Christophe. / FGFR4 signaling is a necessary step in limb muscle differentiation. In: Development. 2002 ; Vol. 129, No. 19. pp. 4559 - 4569.
@article{5d199c6cc993403b9e46f7c02d1e82ee,
title = "FGFR4 signaling is a necessary step in limb muscle differentiation",
abstract = "In chick embryos, most if not all, replicating myoblasts present within the skeletal muscle masses express high levels of the FGF receptor FREK/FGFR4, suggesting an important role for this molecule during myogenesis. We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles. All muscle markers analyzed (such as Myf5, MyoD and the embryonic myosin heavy chain) are affected. We show that inhibition of FGFR4 signal results in an arrest of muscle progenitor differentiation, which can be rapidly reverted by the addition of exogenous FGF, rather than a modification in their proliferative capacities. Conversely, over-expression of FGF8 in somites promotes FGFR4 expression and muscle differentiation in this tissue. Together, these results demonstrate that in vivo, myogenic differentiation is positively controlled by FGF signaling, a notion that contrasts with the general view that FGF promotes myoblast proliferation and represses myogenic differentiation. Our data assign a novel role to FGF8 during chick myogenesis and demonstrate that FGFR4 signaling is a crucial step in the cascade of molecular events leading to terminal muscle differentiation.",
author = "Irene Marics and Francoise Padilla and Jean-Francois Guillemot and Martin Scaal and Christophe Marcelle",
year = "2002",
language = "English",
volume = "129",
pages = "4559 -- 4569",
journal = "Development",
issn = "0950-1991",
publisher = "The Company of Biologists Ltd",
number = "19",

}

Marics, I, Padilla, F, Guillemot, J-F, Scaal, M & Marcelle, C 2002, 'FGFR4 signaling is a necessary step in limb muscle differentiation' Development, vol. 129, no. 19, pp. 4559 - 4569.

FGFR4 signaling is a necessary step in limb muscle differentiation. / Marics, Irene; Padilla, Francoise; Guillemot, Jean-Francois; Scaal, Martin; Marcelle, Christophe.

In: Development, Vol. 129, No. 19, 2002, p. 4559 - 4569.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - FGFR4 signaling is a necessary step in limb muscle differentiation

AU - Marics, Irene

AU - Padilla, Francoise

AU - Guillemot, Jean-Francois

AU - Scaal, Martin

AU - Marcelle, Christophe

PY - 2002

Y1 - 2002

N2 - In chick embryos, most if not all, replicating myoblasts present within the skeletal muscle masses express high levels of the FGF receptor FREK/FGFR4, suggesting an important role for this molecule during myogenesis. We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles. All muscle markers analyzed (such as Myf5, MyoD and the embryonic myosin heavy chain) are affected. We show that inhibition of FGFR4 signal results in an arrest of muscle progenitor differentiation, which can be rapidly reverted by the addition of exogenous FGF, rather than a modification in their proliferative capacities. Conversely, over-expression of FGF8 in somites promotes FGFR4 expression and muscle differentiation in this tissue. Together, these results demonstrate that in vivo, myogenic differentiation is positively controlled by FGF signaling, a notion that contrasts with the general view that FGF promotes myoblast proliferation and represses myogenic differentiation. Our data assign a novel role to FGF8 during chick myogenesis and demonstrate that FGFR4 signaling is a crucial step in the cascade of molecular events leading to terminal muscle differentiation.

AB - In chick embryos, most if not all, replicating myoblasts present within the skeletal muscle masses express high levels of the FGF receptor FREK/FGFR4, suggesting an important role for this molecule during myogenesis. We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles. All muscle markers analyzed (such as Myf5, MyoD and the embryonic myosin heavy chain) are affected. We show that inhibition of FGFR4 signal results in an arrest of muscle progenitor differentiation, which can be rapidly reverted by the addition of exogenous FGF, rather than a modification in their proliferative capacities. Conversely, over-expression of FGF8 in somites promotes FGFR4 expression and muscle differentiation in this tissue. Together, these results demonstrate that in vivo, myogenic differentiation is positively controlled by FGF signaling, a notion that contrasts with the general view that FGF promotes myoblast proliferation and represses myogenic differentiation. Our data assign a novel role to FGF8 during chick myogenesis and demonstrate that FGFR4 signaling is a crucial step in the cascade of molecular events leading to terminal muscle differentiation.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12223412

M3 - Article

VL - 129

SP - 4559

EP - 4569

JO - Development

JF - Development

SN - 0950-1991

IS - 19

ER -

Marics I, Padilla F, Guillemot J-F, Scaal M, Marcelle C. FGFR4 signaling is a necessary step in limb muscle differentiation. Development. 2002;129(19):4559 - 4569.