Home LiteratureArticle Details
PMID: 16380438 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells.

The Journal of cell biology ·Vol. 172 ·No. 1 ·2006-01-02 ·Pages 91-102

Relaix F, Montarras D, Zaffran S, Gayraud-Morel B, Rocancourt D, Tajbakhsh S, Mansouri A, Cumano A, Buckingham M

Abstract

The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context.

MeSH Terms
Animals Apoptosis Cell Cycle Cell Differentiation/genetics Cell Survival/physiology Cells, Cultured Gene Expression Regulation, Developmental/physiology Mice Muscle, Skeletal/cytology Mutation MyoD Protein/metabolism PAX3 Transcription Factor PAX7 Transcription Factor/genetics,physiology Paired Box Transcription Factors/genetics,physiology Satellite Cells, Skeletal Muscle/cytology,physiology
Chemicals
MyoD Protein PAX3 Transcription Factor PAX7 Transcription Factor Paired Box Transcription Factors Pax7 protein, mouse Pax3 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Relaix Frédéric
Unité de Génétique Moléculaire du Développement, Centre National de la Recherche Scientifique URA 2578, Département de Biologie du Développement.
Montarras Didier
Zaffran Stéphane
Gayraud-Morel Barbara
Rocancourt Didier
Tajbakhsh Shahragim
Mansouri Ahmed
Cumano Ana
Buckingham Margaret
References (55)
55 references, click to expand
  1. Enhancement of skeletal muscle regeneration.
    Dev Dyn. 1994 Sep;201(1):41-54 PMID: 7803846
  2. Regulation of Pax-3 expression in the dermomyotome and its role in muscle development.
    Development. 1994 Apr;120(4):957-71 PMID: 7600971
  3. Dysgenesis of cephalic neural crest derivatives in Pax7-/- mutant mice.
    Development. 1996 Mar;122(3):831-8 PMID: 8631261
  4. The role of proteases during apoptosis.
    FASEB J. 1996 Apr;10(5):587-97 PMID: 8621058
  5. Pax3 modulates expression of the c-Met receptor during limb muscle development.
    Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4213-8 PMID: 8633043
  6. Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/- mutant mice.
    Hum Mol Genet. 2000 Jan 1;9(1):1-11 PMID: 10587573
  7. Construction of adenoviral and retroviral vectors coexpressing the genes encoding the hepatitis B surface antigen and B7-1 protein.
    Gene. 1996 Oct 10;175(1-2):121-5 PMID: 8917087
  8. Muscle progenitor cells failing to respond to positional cues adopt non-myogenic fates in myf-5 null mice.
    Nature. 1996 Nov 21;384(6606):266-70 PMID: 8918877
  9. Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD.
    Cell. 1997 Apr 4;89(1):127-38 PMID: 9094721
  10. MyoD, myogenin, and desmin-nls-lacZ transgene emphasize the distinct patterns of satellite cell activation in growth and regeneration.
    Exp Cell Res. 1998 Sep 15;243(2):241-53 PMID: 9743584
  11. Mox2 is a component of the genetic hierarchy controlling limb muscle development.
    Nature. 1999 Jul 1;400(6739):69-73 PMID: 10403250
  12. In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle.
    J Cell Sci. 1999 Sep;112 ( Pt 17):2895-901 PMID: 10444384
  13. Early specification of limb muscle precursor cells by the homeobox gene Lbx1h.
    Nat Genet. 1999 Oct;23(2):213-6 PMID: 10508520
  14. Coordination of cell death and the cell cycle: linking proliferation to death through private and communal couplers.
    Curr Opin Cell Biol. 2004 Dec;16(6):634-8 PMID: 15530774
  15. Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance.
    Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):503-8 PMID: 15623552
  16. Lineage analysis of the avian dermomyotome sheet reveals the existence of single cells with both dermal and muscle progenitor fates.
    Development. 2005 Feb;132(4):689-701 PMID: 15659485
  17. A Pax3/Pax7-dependent population of skeletal muscle progenitor cells.
    Nature. 2005 Jun 16;435(7044):948-53 PMID: 15843801
  18. A common somitic origin for embryonic muscle progenitors and satellite cells.
    Nature. 2005 Jun 16;435(7044):954-8 PMID: 15843802
  19. Pax3/Pax7 mark a novel population of primitive myogenic cells during development.
    Genes Dev. 2005 Jun 15;19(12):1426-31 PMID: 15964993
  20. Identification of nuclei from apoptotic, necrotic, and viable lymphoid cells by using multiparameter flow cytometry.
    Cytometry. 1999 Feb 1;35(2):145-53 PMID: 10554170
  21. Lbx1 is required for muscle precursor migration along a lateral pathway into the limb.
    Development. 2000 Jan;127(2):413-24 PMID: 10603357
  22. The role of Lbx1 in migration of muscle precursor cells.
    Development. 2000 Jan;127(2):437-45 PMID: 10603359
  23. The birth of muscle progenitor cells in the mouse: spatiotemporal considerations.
    Curr Top Dev Biol. 2000;48:225-68 PMID: 10635461
  24. The Ki-67 protein: from the known and the unknown.
    J Cell Physiol. 2000 Mar;182(3):311-22 PMID: 10653597
  25. PAX2 suppresses apoptosis in renal collecting duct cells.
    Am J Pathol. 2000 Sep;157(3):833-42 PMID: 10980123
  26. Pax7 is required for the specification of myogenic satellite cells.
    Cell. 2000 Sep 15;102(6):777-86 PMID: 11030621
  27. Constitutive instability of muscle regulatory factor Myf5 is distinct from its mitosis-specific disappearance, which requires a D-box-like motif overlapping the basic domain.
    Mol Cell Biol. 2000 Dec;20(23):8923-32 PMID: 11073992
  28. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells.
    J Cell Biol. 2000 Dec 11;151(6):1221-34 PMID: 11121437
  29. AmphiPax3/7, an amphioxus paired box gene: insights into chordate myogenesis, neurogenesis, and the possible evolutionary precursor of definitive vertebrate neural crest.
    Evol Dev. 1999 Nov-Dec;1(3):153-65 PMID: 11324100
  30. Cultured myf5 null and myoD null muscle precursor cells display distinct growth defects.
    Biol Cell. 2000 Dec;92(8-9):565-72 PMID: 11374435
  31. Getting your Pax straight: Pax proteins in development and disease.
    Trends Genet. 2002 Jan;18(1):41-7 PMID: 11750700
  32. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis.
    Dev Cell. 2002 Sep;3(3):397-409 PMID: 12361602
  33. Nephric lineage specification by Pax2 and Pax8.
    Genes Dev. 2002 Nov 15;16(22):2958-70 PMID: 12435636
  34. MyoD induces apoptosis in the absence of RB function through a p21(WAF1)-dependent re-localization of cyclin/cdk complexes to the nucleus.
    Oncogene. 2002 Nov 21;21(53):8114-27 PMID: 12444547
  35. The formation of skeletal muscle: from somite to limb.
    J Anat. 2003 Jan;202(1):59-68 PMID: 12587921
  36. Myf5 expression in somites and limb buds of mouse embryos is controlled by two distinct distal enhancer activities.
    Development. 2003 Jul;130(14):3297-307 PMID: 12783799
  37. Correlation of Pax-2 expression with cell proliferation in the developing chicken inner ear.
    J Neurobiol. 2004 Jul;60(1):61-70 PMID: 15188273
  38. Muscle satellite cells adopt divergent fates: a mechanism for self-renewal?
    J Cell Biol. 2004 Aug 2;166(3):347-57 PMID: 15277541
  39. Pax7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification.
    EMBO J. 2004 Aug 18;23(16):3430-9 PMID: 15282552
  40. Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice.
    Nature. 2004 Sep 23;431(7007):466-71 PMID: 15386014
  41. Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal.
    Dev Biol. 2004 Nov 15;275(2):375-88 PMID: 15501225
  42. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts.
    Cell. 1991 Dec 20;67(6):1169-79 PMID: 1836977
  43. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death.
    Cell. 1992 Oct 30;71(3):369-82 PMID: 1423602
  44. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development.
    Cell. 1992 Oct 30;71(3):383-90 PMID: 1330322
  45. Functional domains of the Drosophila Engrailed protein.
    EMBO J. 1993 Jul;12(7):2723-33 PMID: 8334991
  46. The Splotch mutation interferes with muscle development in the limbs.
    Anat Embryol (Berl). 1993 Feb;187(2):153-60 PMID: 8238963
  47. Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells.
    Development. 1994 Mar;120(3):603-12 PMID: 8162858
  48. Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers.
    Dev Biol. 1994 Aug;164(2):588-603 PMID: 7913900
  49. Pax: genes for mice and men.
    Pharmacol Ther. 1994;61(1-2):205-26 PMID: 7938171
  50. Analysis of a key regulatory region upstream of the Myf5 gene reveals multiple phases of myogenesis, orchestrated at each site by a combination of elements dispersed throughout the locus.
    Development. 2003 Aug;130(15):3415-26 PMID: 12810589
  51. Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival.
    Oncogene. 2003 Sep 11;22(39):7989-97 PMID: 12970747
  52. The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo.
    Genes Dev. 2003 Dec 1;17(23):2950-65 PMID: 14665670
  53. Divergent functions of murine Pax3 and Pax7 in limb muscle development.
    Genes Dev. 2004 May 1;18(9):1088-105 PMID: 15132998
  54. Direct isolation of satellite cells for skeletal muscle regeneration.
    Science. 2005 Sep 23;309(5743):2064-7 PMID: 16141372
  55. MyoD is required for myogenic stem cell function in adult skeletal muscle.
    Genes Dev. 1996 May 15;10(10):1173-83 PMID: 8675005
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
2006-01-02
Epub
2005-00-27
Pages
91-102
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2063537
Subset
IM
Corrections
ErratumIn
-
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com