Mechanisms of submucosal gland morphogenesis in the airway.
Submucosal glands (SMGs) are thought to play an important role in the pathogenesis of a number of hypersecretory lung diseases including cystic fibrosis, asthma, and chronic bronchitis. In such diseases, severe SMG hypertrophy and hyperplasia is characteristic of disease progression. Our laboratory has focused efforts on defining both the mechanism of SMG morphogenesis and the identification of SMG stem cells. To this end, we have identified a transcription factor (LEF1) that is temporally and spatially uniquely regulated in SMG progenitors during the initial stages of gland development. LEF1 expression is absolutely required for SMG development in mouse and ferret tracheas, but is insufficient to induce de novo gland development in the absence of other unknown co-factors. In an effort to delineate the transcriptional cascades responsible for inducing LEF1 expression and subsequent SMG development in the airway, we have begun to dissect the regulation of the LEF1 promoter using cell line and transgenic mouse models. Current efforts are focused on defining the cis-acting elements and transcriptional binding factors responsible for Wnt induction of the LEF1 promoter and determining whether the Wnt/beta catenin cascade plays a role in submucosal gland development in vivo.
Filali
Mohammed
M
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.
Liu
Xiaoming
X
Cheng
Ningli
N
Abbott
Duane
D
Leontiev
Vladimir
V
Engelhardt
John F
JF
D000818:Animals; D003598:Cytoskeletal Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005088:Exocrine Glands / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D009093:Mucus / Q000378:metabolism; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012137:Respiratory System / Q000033:anatomy & histology* / Q000196:embryology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin