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.
Department of Anatomy and Neurobiology, Dalhousie University, 5859 University Avenue, B3H 4H7, Halifax, NS, Canada. bkablar@is.dal.ca
Boris
B
Kablar
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