Wnt3a regulates Lef-1 expression during airway submucosal gland morphogenesis

Ryan R Driskell; Michael Goodheart; Traci Neff; Xiaoming Liu; Meihui Luo; Chris Moothart; Curt D Sigmund; Ryoichi Hosokawa; Yang Chai; John F Engelhardt

doi:10.1016/j.ydbio.2007.01.038

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Wnt3a regulates Lef-1 expression during airway submucosal gland morphogenesis

Journal article

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Wnt3a regulates Lef-1 expression during airway submucosal gland morphogenesis

Ryan R Driskell, Michael Goodheart, Traci Neff, Xiaoming Liu, Meihui Luo, Chris Moothart, Curt D Sigmund, Ryoichi Hosokawa, Yang Chai and John F Engelhardt

Developmental Biology, Vol.305(1), pp.90-102

2007

DOI: 10.1016/j.ydbio.2007.01.038

PMCID: PMC1892170

PMID: 17335794

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Abstract

Regulation of the lymphoid enhancer factor 1 (Lef-1) transcription factor is important for the inductive formation of many epithelial-derived appendages including airway submucosal glands (SMGs). Although Wnts have been linked to developmental processes involving transcriptional activation of the Lef-1 protein, there is little in vivo information directly linking Wnts with the transcriptional regulation of the Lef-1 promoter. In the present study, we hypothesized that Wnt3a directly regulates Lef-1 gene expression required for SMG morphogenesis in mice. In support of this hypothesis, TOPGAL reporter mice demonstrated activation of β-catenin/Tcf complexes during early phases of SMG development and immunolocalization studies confirmed abundant expression of Tcf4, but not Tcf1 or Tcf3, at this stage. ChIP analysis in primary airway epithelial cells revealed that Tcf4 associates with a known Wnt Responsive Region in the Lef-1 promoter and transfection of Cos-1 cells with dominant active β-catenin and Tcf4 synergistically activated the Lef-1 promoter. Using Wnt3a deficient and Lef-1 promoter-GFP reporter mice, we also demonstrate that Wnt3a induces Lef-1 gene expression in newly forming SMG buds of mice and is required for the maintenance of gland bud growth. These findings provide the first in vivo evidence that Wnt3a can transcriptionally regulate the Lef-1 gene.

Wnt3a

Glands

TOPGAL

Development

Tcf4

Airway

Lef-1

Details

Title: Subtitle: Wnt3a regulates Lef-1 expression during airway submucosal gland morphogenesis
Creators: Ryan R Driskell - Department of Anatomy and Cell Biology, Iowa City, IA 52242, USA
Michael Goodheart - Department of Obstetrics and Gynecology, Iowa City, IA 52242, USA
Traci Neff - Department of Obstetrics and Gynecology, Iowa City, IA 52242, USA
Xiaoming Liu - Department of Anatomy and Cell Biology, Iowa City, IA 52242, USA
Meihui Luo - Department of Anatomy and Cell Biology, Iowa City, IA 52242, USA
Chris Moothart - Department of Anatomy and Cell Biology, Iowa City, IA 52242, USA
Curt D Sigmund - Department of Internal Medicine, Iowa City, IA 52242, USA
Ryoichi Hosokawa - Center for Craniofacial Molecular Biology, University of Southern California, USA
Yang Chai - Center for Craniofacial Molecular Biology, University of Southern California, USA
John F Engelhardt - Department of Anatomy and Cell Biology, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Developmental Biology, Vol.305(1), pp.90-102
DOI: 10.1016/j.ydbio.2007.01.038
PMID: 17335794
PMCID: PMC1892170
NLM abbreviation: Dev Biol
ISSN: 0012-1606
eISSN: 1095-564X
Publisher: Elsevier Inc
Language: English
Date published: 2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Radiation Oncology; Obstetrics and Gynecology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9983931734802771

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