The regulatory mechanisms that underlie inappropriate transcription of the myogenic determination gene Myf5 in the central nervous system.
Myf5 is a key myogenic determination factor, specifically present at sites of myogenesis. Surprisingly, during mouse development, this gene is also transcribed in restricted areas of the central nervous system, although the Myf5 protein is not detectable. We have investigated the regulation of Myf5 expression in the central nervous system. Using both in ovo electroporation in the chick embryo and transgenesis in the mouse, we show that regulatory sequences that direct neuronal Myf5 transcription are present in a distal element located between -55 and -54.3 Kb from the Myf5 gene. An Oct6/Tst1 binding site is required for embryonic brain expression, and in the Oct6 mutant mouse embryo, Myf5 transcripts are no longer detectable in the brain. The Wnt-beta catenin signalling pathway is also implicated. Finally we show that post-transcriptional regulation of Myf5 gene expression involves miRNA repression acting through the Myf5-3'UTR.
Daubas
Philippe
P
Institut Pasteur, CNRS URA 2578, Department of Developmental Biology, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Crist
Colin G
CG
Bajard
Lola
L
Relaix
Frédéric
F
Pecnard
Emmanuel
E
Rocancourt
Didier
D
Buckingham
Margaret
M
D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000254:growth & development; D002642:Chick Embryo; D018274:Electroporation; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology; D024510:Muscle Development / Q000235:genetics; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional; D014157:Transcription Factors; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism
D020413:3' Untranslated Regions; D035683:MicroRNAs; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D014157:Transcription Factors; D051153:Wnt Proteins