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| Status |
Public on Apr 15, 2008 |
| Title |
Genes regulated by GATA6 in the lung |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Epithelial organs including the lung are known to possess regenerative abilities through activation of endogenous stem cell populations but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation in Gata6 null lung epithelium. This expansion of BASCs is the result of a dramatic increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the non-canonical Wnt receptor Fzd2 is down-regulated in Gata6 mutants and increased Fzd2 or decreased β-catenin expression rescues, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, we show that canonical Wnt signaling is activated in the niche containing BASCs and forced activation of Wnt signaling leads to a dramatic increase in BASC numbers. Moreover, Gata6 is required for proper lung epithelial regeneration and postnatal loss of Gata6 leads to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6 regulated Wnt signaling controls the balance between stem/progenitor expansion and epithelial differentiation required for both lung development and regeneration.
Keywords: gene targets in knockout mouse model
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| |
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| Overall design |
3 replicates of each condition-wild-type and GATA6 null tissue. 6 total samples.
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| |
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| Contributor(s) |
Morrisey EE |
| Citation(s) |
18536717 |
| |
| Submission date |
Apr 14, 2008 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Edward Morrisey |
| E-mail(s) |
[email protected]
|
| Phone |
215-573-3010
|
| Fax |
215-573-2094
|
| Organization name |
University of Pennsylvania
|
| Department |
Medicine and Cell and Developmental Biology
|
| Street address |
941 Curie Blvd.
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (6)
|
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| Relations |
| BioProject |
PRJNA106857 |
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