A 5.5-kb enhancer is both necessary and sufficient for regulation of Wnt-1 transcription in vivo.
Wnt-1 encodes a secreted signaling molecule which is required for development of the midbrain and anterior hindbrain in the mouse. Wnt-1 expression is initiated early in the development of the central nervous system in a region predicted to give rise to the midbrain. Later in development Wnt-1 expression is restricted to regions of the forebrain, midbrain, and spinal cord. Previous studies identified a 5.5-kb enhancer in the Wnt-1 locus which is sufficient to activate transcription of a reporter gene in a pattern very similar to that of the endogenous Wnt-1 gene. Here we have assessed if this enhancer is an important component of the endogenous regulatory sequences of Wnt-1 by gene targeting and by testing if it is able to express Wnt-1 in a pattern which is sufficient to rescue the phenotype of loss of Wnt-1. Our results show that the 5.5-kb enhancer is both necessary and sufficient for Wnt-1 expression in vivo.
Danielian
P S
PS
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Echelard
Y
Y
Vassileva
G
G
McMahon
A P
AP
D000818:Animals; D004742:Enhancer Elements, Genetic; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005816:Genetic Complementation Test; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D014158:Transcription, Genetic; D019076:Transgenes; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D005326:Fetal Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins