Wnt-responsive element controls Lef-1 promoter expression during submucosal gland morphogenesis.
Regulated expression of lymphoid enhancer factor 1 (Lef-1) plays an obligatory role in the transcriptional control of epithelial bud formation during airway submucosal gland and mammary gland development. However, regions of the Lef-1 promoter required for spatial and temporal regulation during glandular development have yet to be defined. We hypothesized that a previously reported 110-bp Wnt-responsive element (WRE) in the Lef-1 promoter, which can be induced by Wnt-3a/beta-catenin signals, may also play a role in regulating Lef-1 expression during airway and mammary gland development. Here we show that the Lef-1 promoter is also responsive to Wnt-1 signals in both airway and mammary epithelial cell lines. To better understand the importance of the WRE in dynamically regulating Lef-1 promoter activation in these two types of epithelia in vivo, we utilized LacZ reporter transgenic mice to evaluate the significance of Wnt-responsive sequences in the Lef-1 promoter during glandular bud formation. A 2.5-kb Lef-1 promoter fragment partially reproduced endogenous Lef-1 expression patterns in a subset of cell types involved in both mammary gland and submucosal glandular bud development. Interestingly, removal of the 110-bp WRE from the Lef-1 promoter ablated expression in nasal and tracheal submucosal glandular buds while having no significant effect on developmental expression in mammary glandular buds. These findings suggest that Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation.
Driskell
Ryan R
RR
Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Liu
Xiaoming
X
Luo
Meihui
M
Filali
Mohammed
M
Zhou
Weihong
W
Abbott
Duane
D
Cheng
Ningli
N
Moothart
Chris
C
Sigmund
Curt D
CD
Engelhardt
John F
JF
D000818:Animals; D001483:Base Sequence; D001940:Breast; D001943:Breast Neoplasms; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D001616:beta-Galactosidase / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D011505:Protein-Tyrosine Kinases; D001616:beta-Galactosidase