Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm
<p>Abstract</p> <p>Background</p> <p>Studies in many model systems have shown that canonical signaling through the pathway downstream of ligands of the Wnt family can regulate multiple steps in organogenesis, including cell proliferation, differentiation, and lineage sp...
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| Format: | Article |
| Language: | English |
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BMC
2004-06-01
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| Series: | Journal of Biology |
| Online Access: | http://jbiol.com/content/3/3/11 |
| _version_ | 1811250925106364416 |
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| author | Hogan Brigid LM Okubo Tadashi |
| author_facet | Hogan Brigid LM Okubo Tadashi |
| author_sort | Hogan Brigid LM |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Studies in many model systems have shown that canonical signaling through the pathway downstream of ligands of the Wnt family can regulate multiple steps in organogenesis, including cell proliferation, differentiation, and lineage specification. In addition, misexpression of the Wnt-family member Wingless in <it>Drosophila </it>imaginal disc cells can lead to transdetermination of progenitors from one lineage to another. Conditional deletion of the β-catenin component of the Wnt signaling pathway has indicated a role for Wnt signaling in mouse lung endoderm development. The full range of effects of this pathway, which includes the transcription factor Lef1, has not been explored, however.</p> <p>Results</p> <p>To explore this issue, we expressed a constitutively active β-catenin-Lef1 fusion protein in transgenic embryos using a lung-endoderm-specific promoter from the <it>surfactant protein C </it>gene. Transgenic lungs appeared grossly normal, but internally they contained highly proliferative, cuboidal epithelium lacking fully differentiated lung cell types. Unexpectedly, microarray analysis and <it>in situ </it>hybridization revealed a mosaic of cells expressing marker genes characteristic of intestinal Paneth and goblet cells and other non-lung secretory cell types. In addition, there was strong ectopic expression of genes such as <it>Cdx1 </it>and <it>Atoh1 </it>that normally regulate gut development and early allocation of cells to intestinal secretory lineages.</p> <p>Conclusions</p> <p>Our results show that hyperactive Wnt signaling in lung progenitors expressing a lung-specific gene can induce a dramatic switch in lineage commitment and the generation of intestinal cell types. We discuss the relevance of our findings to the poorly understood pathological condition of intestinal metaplasia in humans.</p> |
| first_indexed | 2024-04-12T16:12:04Z |
| format | Article |
| id | doaj.art-a98b0707c884410a862524daabc9a684 |
| institution | Directory Open Access Journal |
| issn | 1478-5854 1475-4924 |
| language | English |
| last_indexed | 2024-04-12T16:12:04Z |
| publishDate | 2004-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biology |
| spelling | doaj.art-a98b0707c884410a862524daabc9a6842022-12-22T03:25:53ZengBMCJournal of Biology1478-58541475-49242004-06-01331110.1186/jbiol3Hyperactive Wnt signaling changes the developmental potential of embryonic lung endodermHogan Brigid LMOkubo Tadashi<p>Abstract</p> <p>Background</p> <p>Studies in many model systems have shown that canonical signaling through the pathway downstream of ligands of the Wnt family can regulate multiple steps in organogenesis, including cell proliferation, differentiation, and lineage specification. In addition, misexpression of the Wnt-family member Wingless in <it>Drosophila </it>imaginal disc cells can lead to transdetermination of progenitors from one lineage to another. Conditional deletion of the β-catenin component of the Wnt signaling pathway has indicated a role for Wnt signaling in mouse lung endoderm development. The full range of effects of this pathway, which includes the transcription factor Lef1, has not been explored, however.</p> <p>Results</p> <p>To explore this issue, we expressed a constitutively active β-catenin-Lef1 fusion protein in transgenic embryos using a lung-endoderm-specific promoter from the <it>surfactant protein C </it>gene. Transgenic lungs appeared grossly normal, but internally they contained highly proliferative, cuboidal epithelium lacking fully differentiated lung cell types. Unexpectedly, microarray analysis and <it>in situ </it>hybridization revealed a mosaic of cells expressing marker genes characteristic of intestinal Paneth and goblet cells and other non-lung secretory cell types. In addition, there was strong ectopic expression of genes such as <it>Cdx1 </it>and <it>Atoh1 </it>that normally regulate gut development and early allocation of cells to intestinal secretory lineages.</p> <p>Conclusions</p> <p>Our results show that hyperactive Wnt signaling in lung progenitors expressing a lung-specific gene can induce a dramatic switch in lineage commitment and the generation of intestinal cell types. We discuss the relevance of our findings to the poorly understood pathological condition of intestinal metaplasia in humans.</p>http://jbiol.com/content/3/3/11 |
| spellingShingle | Hogan Brigid LM Okubo Tadashi Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm Journal of Biology |
| title | Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm |
| title_full | Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm |
| title_fullStr | Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm |
| title_full_unstemmed | Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm |
| title_short | Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm |
| title_sort | hyperactive wnt signaling changes the developmental potential of embryonic lung endoderm |
| url | http://jbiol.com/content/3/3/11 |
| work_keys_str_mv | AT hoganbrigidlm hyperactivewntsignalingchangesthedevelopmentalpotentialofembryoniclungendoderm AT okubotadashi hyperactivewntsignalingchangesthedevelopmentalpotentialofembryoniclungendoderm |