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Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice.
Nature. 2004 Sep 23; 431(7007):466-71.Nat

Abstract

In vertebrates, skeletal muscle is a model for the acquisition of cell fate from stem cells. Two determination factors of the basic helix-loop-helix myogenic regulatory factor (MRF) family, Myf5 and Myod, are thought to direct this transition because double-mutant mice totally lack skeletal muscle fibres and myoblasts. In the absence of these factors, progenitor cells remain multipotent and can change their fate. Gene targeting studies have revealed hierarchical relationships between these and the other MRF genes, Mrf4 and myogenin, where the latter are regarded as differentiation genes. Here we show, using an allelic series of three Myf5 mutants that differentially affect the expression of the genetically linked Mrf4 gene, that skeletal muscle is present in the new Myf5:Myod double-null mice only when Mrf4 expression is not compromised. This finding contradicts the widely held view that myogenic identity is conferred solely by Myf5 and Myod, and identifies Mrf4 as a determination gene. We revise the epistatic relationship of the MRFs, in which both Myf5 and Mrf4 act upstream of Myod to direct embryonic multipotent cells into the myogenic lineage.

Authors+Show Affiliations

Kassar-Duchossoy L
Stem Cells and Development, Department of Developmental Biology, CNRS URA 2578, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Gayraud-Morel B
No affiliation info available
Gomès D
No affiliation info available
Rocancourt D
No affiliation info available
Buckingham M
No affiliation info available
Shinin V
No affiliation info available
Tajbakhsh S
No affiliation info available

MeSH

AllelesAnimalsCell DifferentiationCell LineageDNA-Binding ProteinsEmbryo, MammalianGene DeletionGene Expression Regulation, DevelopmentalMiceMice, KnockoutMuscle ProteinsMuscle, SkeletalMyoD ProteinMyogenic Regulatory Factor 5Myogenic Regulatory FactorsMyogeninRNA, MessengerTrans-Activators

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15386014

Citation

Kassar-Duchossoy, Lina, et al. "Mrf4 Determines Skeletal Muscle Identity in Myf5:Myod Double-mutant Mice." Nature, vol. 431, no. 7007, 2004, pp. 466-71.
Kassar-Duchossoy L, Gayraud-Morel B, Gomès D, et al. Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature. 2004;431(7007):466-71.
Kassar-Duchossoy, L., Gayraud-Morel, B., Gomès, D., Rocancourt, D., Buckingham, M., Shinin, V., & Tajbakhsh, S. (2004). Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature, 431(7007), 466-71.
Kassar-Duchossoy L, et al. Mrf4 Determines Skeletal Muscle Identity in Myf5:Myod Double-mutant Mice. Nature. 2004 Sep 23;431(7007):466-71. PubMed PMID: 15386014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. AU - Kassar-Duchossoy,Lina, AU - Gayraud-Morel,Barbara, AU - Gomès,Danielle, AU - Rocancourt,Didier, AU - Buckingham,Margaret, AU - Shinin,Vasily, AU - Tajbakhsh,Shahragim, PY - 2004/03/13/received PY - 2004/07/23/accepted PY - 2004/9/24/pubmed PY - 2004/10/6/medline PY - 2004/9/24/entrez SP - 466 EP - 71 JF - Nature JO - Nature VL - 431 IS - 7007 N2 - In vertebrates, skeletal muscle is a model for the acquisition of cell fate from stem cells. Two determination factors of the basic helix-loop-helix myogenic regulatory factor (MRF) family, Myf5 and Myod, are thought to direct this transition because double-mutant mice totally lack skeletal muscle fibres and myoblasts. In the absence of these factors, progenitor cells remain multipotent and can change their fate. Gene targeting studies have revealed hierarchical relationships between these and the other MRF genes, Mrf4 and myogenin, where the latter are regarded as differentiation genes. Here we show, using an allelic series of three Myf5 mutants that differentially affect the expression of the genetically linked Mrf4 gene, that skeletal muscle is present in the new Myf5:Myod double-null mice only when Mrf4 expression is not compromised. This finding contradicts the widely held view that myogenic identity is conferred solely by Myf5 and Myod, and identifies Mrf4 as a determination gene. We revise the epistatic relationship of the MRFs, in which both Myf5 and Mrf4 act upstream of Myod to direct embryonic multipotent cells into the myogenic lineage. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/15386014/Mrf4_determines_skeletal_muscle_identity_in_Myf5:Myod_double_mutant_mice_ DB - PRIME DP - Unbound Medicine ER -