Different regulatory elements within the MyoD promoter control its expression in the brain and inhibit its functional consequences in neurogenesis.
MyoD is a key basic helix-loop-helix (bHLH) transcription factor capable of converting many cells into skeletal muscle. Together with Myf5 it is essential for initiating skeletal myogenesis. In this report, the restricted domains of MyoD-lacZ expression have been revealed in the embryonic mouse brain by the analysis of transgenic mice with reporter genes driven by MyoD regulatory elements. The MD6.0-lacZ transgene was localized in the basal plate of pons, medulla oblongata (i.e. the medial longitudinal fasciculus) and spinal cord of wild-type and mutant mouse embryos at various stages of development, whereas the 258/-2.5lacZ transgene was not detected in the brain. In addition, MyoD RNA and MyoD protein accumulations were monitored in neurons expressing MD6.0-lacZ transgene. Although MyoD was detected in muscle myotomal cells, it was absent in MD6.0-lacZ-expressing neurons. This would account for the lack of myogenic conversion in brain structures and the absence of a neural phenotype in MyoD-/- embryos and mice. Together, these data indicate that within the promoter of MyoD different regulatory elements control its expression and prevent the functional consequences of MyoD in neurogenesis.
Kablar
Boris
B
Department of Anatomy and Neurobiology, Dalhousie University, 5859 University Avenue, B3H 4H7, Halifax, NS, Canada. bkablar@is.dal.ca
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D017570:MyoD Protein / Q000096:biosynthesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D017570:MyoD Protein; D012333:RNA, Messenger; D001616:beta-Galactosidase