Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues

Besnard, Valérie; Wert, Susan E.; Hull, William M.; Whitsett, Jeffrey A.

doi:10.1016/j.modgep.2004.08.006

Cited by 187 publications

(161 citation statements)

References 30 publications

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“…Foxa2 is important for alveolarization of the lungs during development (Wan et al 2004). Adult lungs express Foxa2 in the bronchiolar epithelium and alveolar type II cells (Besnard et al 2004). Interestingly, while Foxa2 expression and function overlap largely with Foxa1, we did not see differential expression of Foxa1 between T nonMet and T Met /Met cells (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 75%

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Gocheva

Oudin

et al. 2015

Genes Dev.

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Despite the fact that the majority of lung cancer deaths are due to metastasis, the molecular mechanisms driving metastatic progression are poorly understood. Here, we present evidence that loss of Foxa2 and Cdx2 synergizes with loss of Nkx2-1 to fully activate the metastatic program. These three lineage-specific transcription factors are consistently down-regulated in metastatic cells compared with nonmetastatic cells. Knockdown of these three factors acts synergistically and is sufficient to promote the metastatic potential of nonmetastatic cells to that of naturally arising metastatic cells in vivo. Furthermore, silencing of these three transcription factors is sufficient to account for a significant fraction of the gene expression differences between the nonmetastatic and metastatic states in lung adenocarcinoma, including up-regulated expression of the invadopodia component Tks5 long , the embryonal protooncogene Hmga2, and the epithelial-to-mesenchymal mediator Snail. Finally, analyses of tumors from a genetically engineered mouse model and patients show that low expression of Nkx2-1, Foxa2, and Cdx2 strongly correlates with more advanced tumors and worse survival. Our findings reveal that a large part of the complex transcriptional network in metastasis can be controlled by a small number of regulatory nodes that function redundantly, and loss of multiple nodes is required to fully activate the metastatic program.[Keywords: lung adenocarcinoma; metastasis; Nkx2-1; Foxa2; Cdx2; genetically engineered mouse model of cancer] Supplemental material is available for this article.

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Section: Discussionmentioning

confidence: 75%

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Gocheva

Oudin

et al. 2015

Genes Dev.

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“…Thereafter, Foxa2 is present in the notochord, gut endoderm, and ventral midline of the central nervous system. Later in embryonic development, Foxa2 is detected in organs derived from the foregut endoderm and the hindgut endoderm (10 -12), tissues of ectodermal and mesodermal origins, and endodermally derived epithelial cells in the lung (13). Foxa1 mRNA is detected in the endoderm during the late primitive streak stage of development in the mice.…”

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confidence: 99%

Compensatory Roles of Foxa1 and Foxa2 during Lung Morphogenesis

Wan

Dingle

et al. 2005

Journal of Biological Chemistry

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Lung morphogenesis begins with a ventral out-pouching of endodermally derived cells from the anterior foregut into the surrounding mesenchyme at E9 -9.5 1 in the mouse. Lung tubules are formed by branching morphogenesis as respiratory epithelial cells proliferate and differentiate to form the conducting airways. Thereafter, terminal airways sacculate and septate to form the alveoli typical of the peripheral lung. The ordered process mediating branching morphogenesis and the formation of the alveoli are regulated by the precise temporalspatial expression of many transcription factors, including Gata6, Ttf1, and forkhead transcription factors, including Foxa1, Foxa2, Foxj1, Foxf1, Foxp1, and Foxp2, that regulate gene expression and influence cell differentiation in the lung (1-6).Foxa (previously termed HNF3) transcription factors comprise a subfamily of forkhead transcription factors that share Ͼ90% homology in the winged helix DNA binding domain.

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“…Here, we have demonstrated that FoxA1 mRNA and protein levels are upregulated in rat lung tissue following treatment with OA, suggesting a potential role for FoxA1 in OA-induced ALI. In the adult lung, FoxA1 is expressed in epithelial cells of conducting airways and in AT-2 cells [19]. In addition to being targeted by pathogens, inflammatory cells, and mediators, epithelial cells are also actively involved in the regulation of the inflammatory response [39,40].…”

Section: Discussionmentioning

confidence: 99%

“…During formation of the definitive endoderm, FoxA1 is detected in the notochord and floor plate [15][16][17][18]. Later in embryonic development and in adulthood, FoxA1 is detected in tissues of endodermal, ectodermal, and mesodermal origin [19][20][21]. In the lung, FoxA1 and FoxA2 are first expressed at the onset of lung bud formation and expression persists in the adult lung, where FoxA1 and FoxA2 are coexpressed in epithelial cells in conducting airways and in alveolar type II epithelial cells (AT-2 cells) [19].…”

Section: Introductionmentioning

confidence: 99%

“…Later in embryonic development and in adulthood, FoxA1 is detected in tissues of endodermal, ectodermal, and mesodermal origin [19][20][21]. In the lung, FoxA1 and FoxA2 are first expressed at the onset of lung bud formation and expression persists in the adult lung, where FoxA1 and FoxA2 are coexpressed in epithelial cells in conducting airways and in alveolar type II epithelial cells (AT-2 cells) [19]. Although FoxA1 is not required for respiration at birth, deletion of FoxA1 influences lung morphogenesis and epithelial cell differentiation at distinct times during perinatal development.…”

Section: Introductionmentioning

confidence: 99%

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A Role for Forkhead Box A1 in Acute Lung Injury

et al. 2009

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Abstract-Forkhead box protein A1 (FoxA1) is an evolutionarily conserved winged helix transcription factor with diverse regulatory functions. However, little is known about the role of FoxA1 in acute lung injury (ALI) and pulmonary cell injury. In this study, an in vivo model was employed whereby rats were administered an intravenous injection of oleic acid (OA, 0.1 ml/kg), and alveolar type II epithelial cells (AT-2 cells) injury was induced by hydrogen peroxide (H 2 O 2 ) in vitro. OA injection resulted in lung injury and AT-2 cells apoptosis in vivo. OA injection and H 2 O 2 upregulated FoxA1 mRNA and protein in lung tissue of the in vivo ALI model and in H 2 O 2 challenged AT-2 cells. Overexpression of FoxA1 promoted apoptosis, whereas FoxA1 deficiency, induced by antisense oligonucleotides, decreased AT-2 cells apoptosis induced by H 2 O 2 , as shown by flow cytometry. These results suggest that FoxA1 may play an important role in ALI by promoting apoptosis of pulmonary epithelial cells.KEY WORDS: acute lung injury; forkhead box A1; apoptosis.

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Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues

Cited by 187 publications

References 30 publications

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Compensatory Roles of Foxa1 and Foxa2 during Lung Morphogenesis

A Role for Forkhead Box A1 in Acute Lung Injury

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