CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT

CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT

Bibliographic Details
Main Author: WAN, HUAJING
Language:English
Published: University of Cincinnati / OhioLINK 2004
Subjects:
Lung
forkhead
winged helix
transcription factor
development
pulmonary epithelium
surfactant
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1091650603
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin10916506032021-08-03T06:09:46Z CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT WAN, HUAJING Lung forkhead winged helix transcription factor development pulmonary epithelium surfactant The winged helix transcription factor, Foxa2 is expressed in the foregut endoderm and in subsets of respiratory epithelial cells in the fetal and adult lung. Because the targeted mutagenesis of Foxa2 gene in mice is lethal before formation of the lung, its potential roles in lung morphogenesis and homeostasis has not been determined. In order to discern the role of Foxa2 in epithelial cell differentiation and pulmonary adaptation at birth, triple transgenic mice (Foxa2Flx/Flx, SPC-rtTA, (TetO)7-cre and Foxa2Flx/Flx, CCSP-rtTA, (TetO)7-cre) were generated in which Foxa2 was selectively deleted in the respiratory epithelial cells of the developing lung. Although lobulation and early branching morphogenesis were normal, decreased lung to body ratio, arrested epithelial cell differentiation and abnormalities in syntheses of surfactant proteins and lipids were observed prior to birth. When observed during normal delivery (E19.5-20), approximately 50% of the Foxa2 delta/delta mice developed respiratory failure within 2-3 hours after birth. Histologic examination of the pups found in distress or moribund, revealed atelectasis, with extensive formation of hyaline membranes lining terminal airways, typical of findings in preterm infants with RDS. Goblet cell hyperplasia, mucin production, inflammation and airspace abnormalities were observed in Foxa2 delta/delta; mice postnatally and all of the Foxa2 delta/delta mice will die before PN60. Morphological, biochemical and functional analysis of the Foxa2 delta/delta mice indicated that Foxa2 is the first gene shown to regulate the complex program of pulmonary maturation required for transition to air breathing at birth and normal lung function after birth through direct and indirect transcriptional regulation of genes mediating surfactant homeostasis and host defense. Foxa1 and Foxa2 are co-expressed in subsets of respiratory epithelial cells during lung morphogenesis. Similarity of the expression patterns and conservation of their DNA binding domains indicate that they may share overlapping functions during development. Deletion of both Foxa1 and Foxa2 disrupted lung branching morphogenesis and epithelial cell differentiation, indicating that Foxa1 and Foxa2 play overlapping roles in the process of branching morphogenesis and epithelial cell differentiation of the lung. 2004-10-07 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1091650603 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1091650603 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Lung
forkhead
winged helix
transcription factor
development
pulmonary epithelium
surfactant
spellingShingle Lung
forkhead
winged helix
transcription factor
development
pulmonary epithelium
surfactant
WAN, HUAJING
CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT
author WAN, HUAJING
author_facet WAN, HUAJING
author_sort WAN, HUAJING
title CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT
title_short CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT
title_full CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT
title_fullStr CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT
title_full_unstemmed CRITICAL ROLES OF FORKHEAD BOX A2 DURING LUNG DEVELOPMENT
title_sort critical roles of forkhead box a2 during lung development
publisher University of Cincinnati / OhioLINK
publishDate 2004
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1091650603
work_keys_str_mv AT wanhuajing criticalrolesofforkheadboxa2duringlungdevelopment
_version_ 1719431960041881600

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