Six and Eya expression during human somitogenesis and MyoD gene family activation.
This report describes the characterisation of the expression profile of several myogenic determination genes during human embryogenesis. The data were obtained from axial structures and limb buds of human embryos aged between 3 and 8 weeks of development. Using in situ hybridisation to detect Pax3 and MyoD gene family mRNAs, and immunochemistry to follow Six and Eya protein accumulation, we have been able to establish the chronology of accumulation of these gene products. As in mouse, the first transcripts detected in myotomes of 3 week-old embryos are Pax3 and Myf5, followed by the expression of myogenin. MyoD appears to be activated well after Myf5, myogenin and MRF4 in the early myotome, whereas, in limb bud muscles, the presence of all four of these mRNAs is concomitant from 6 weeks. Six1, Six4 and Six5 homeoproteins are detected later than Myf5 activation. These Six homeoproteins are first observed in the cytoplasm of myogenin expressing cells. At later stages of development, Six1 and Six5, but not Six4, are translocated into the nuclei of myogenic cells, concomitantly with MyHCemb expression. Eya1 and Eya2 proteins, potential Six cofactors, were also detected in myogenin positive cells, but their accumulation was delayed and was mainly cytoplasmic. These results preclude that early activation of Myf5, myogenin and MRF4 is under the control of Six and Eya proteins, while Six and Eya proteins would be involved in later steps of myogenic differentiation.
Fougerousse
Françoise
F
URA CNRS 1923, Généthon, 1 rue de l'Internationale, BP60, 91002 Evry, France. fougerou@genethon.fr
Durand
Muriel
M
Lopez
Soledad
S
Suel
Laurence
L
Demignon
Josiane
J
Thornton
Charles
C
Ozaki
Hidenori
H
Kawakami
Kyoshi
K
Barbet
Patrick
P
Beckmann
Jacques S
JS
Maire
Pascal
P
D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics*; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000235:genetics; D018008:Myogenin / Q000235:genetics; D009687:Nuclear Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D017027:Protein Tyrosine Phosphatases; D012333:RNA, Messenger / Q000378:metabolism; D019170:Somites / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C497417:MYF5 protein, human; C503799:MYOG protein, human; D009124:Muscle Proteins; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D009687:Nuclear Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms; D012333:RNA, Messenger; C099236:SIX1 protein, human; C490947:Six1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C063403:myogenic factor 6; C068686:Pax3 protein, mouse; C104381:EYA1 protein, human; C501156:Eya1 protein, mouse; D017027:Protein Tyrosine Phosphatases