Identification of a hypaxial somite enhancer element regulating Pax3 expression in migrating myoblasts and characterization of hypaxial muscle Cre transgenic mice.
Pax3 encodes a transcription factor that functions in the embryonic central nervous system, neural crest, and somitic mesoderm. Prior studies suggest that distinct regulatory elements regulate temporal and spatial expression of Pax3 in neural crest and mesoderm. Here, we describe a discrete enhancer element, conserved between mouse and human genomes, that directs Pax3 expression in the ventral-lateral lip of interlimb somites. These regions give rise to hypaxial musculature including limb, ventral body wall, diaphragm, and tongue muscles. Transgenic mice harboring the hypaxial muscle enhancer driving lacZ expression initiate beta-galactosidase expression at E10.0, significantly later than endogenous Pax3 expression in presomitic and segmented mesoderm. Initiation of transgene expression is not dependent on Pax3 itself, since expression is detectable in homozygous Splotch embryos. Transgenic mice expressing Cre recombinase in hypaxial myoblasts were generated and characterized. These results suggest that Pax3 is differentially regulated within the somite in both spatial and temporal domains. Hypaxial muscle Cre mice will allow for specific manipulation of gene expression in this subset of developing skeletal muscle.
Brown
Christopher B
CB
Cardiovascular Division, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Engleka
Kurt A
KA
Wenning
Jennifer
J
Min Lu
Min
M
Epstein
Jonathan A
JA
D000818:Animals; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000196:embryology*; D032446:Myoblasts / Q000502:physiology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D019170:Somites; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*
D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse; C045073:Cre recombinase; D019426:Integrases