Jeffrey A. Whitsett

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The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons(More)
To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4b(G12D) under the control of doxycycline in type II pneumocytes. Focal proliferative lesions of alveolar type II pneumocytes were observed as early as seven days after induction with(More)
The goal of this study was to determine the changes that occur in surfactant-associated proteins in bronchoalveolar lavage fluid (BAL) and serum of patients at risk for ARDS and during the course of ARDS. We found that the concentrations of SP-A and SP-B were low in the BAL of patients at risk for ARDS before the onset of clinically defined lung injury,(More)
Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought to determine if endogenous surfactant is altered in ARDS. Bronchoalveolar lavage was performed in patients at-risk to develop ARDS (AR, n = 20), with ARDS (A, n = 66) and in normal subjects (N, n = 29). The crude surfactant(More)
BACKGROUND Pulmonary surfactant forms a lipid-rich monolayer that coats the airways of the lung and is essential for proper inflation and function of the lung. Surfactant is produced by alveolar type II cells, stored intracellularly in organelles known as lamellar bodies, and secreted by exocytosis. The gene for ATP-binding cassette transporter A3 (ABCA3)(More)
Herein, we demonstrate that Lrp6-mediated R-spondin 2 signaling through the canonical Wnt pathway is required for normal morphogenesis of the respiratory tract and limbs. We show that the footless insertional mutation creates a severe hypomorphic R-spondin 2 allele (Rspo2(Tg)). The predicted protein encoded by Rspo2(Tg) neither bound the cell surface nor(More)
Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the(More)
The lungs are divided, both structurally and functionally, into two distinct components, the proximal airways, which conduct air, and the peripheral airways, which mediate gas exchange. The mechanisms that control the specification of these two structures during lung development are currently unknown. Here we show that beta-catenin signaling is required for(More)
Murine lung epithelial (MLE) cell lines representing the distal bronchiolar and alveolar epithelium were produced from lung tumors generated in transgenic mice harboring the viral oncogene simian virus 40 (SV40) large tumor antigen under transcriptional control of a promoter region from the human surfactant protein C (SP-C) gene. The cell lines exhibited(More)
The ventral pancreas, biliary system, and liver arise from the posterior ventral foregut, but the cell-intrinsic pathway by which these organ lineages are separated is not known. Here we show that the extrahepatobiliary system shares a common origin with the ventral pancreas and not the liver, as previously thought. These pancreatobiliary progenitor cells(More)