| First Author | Perl AK | Year | 2003 |
| Journal | Dev Biol | Volume | 258 |
| Issue | 1 | Pages | 154-68 |
| PubMed ID | 12781690 | Mgi Jnum | J:83751 |
| Mgi Id | MGI:2663389 | Doi | 10.1016/s0012-1606(03)00106-4 |
| Citation | Perl AK, et al. (2003) Temporal effects of Sprouty on lung morphogenesis. Dev Biol 258(1):154-68 |
| abstractText | Paracrine signaling mediated by FGF-10 and the FGF-R2IIIb receptor is required for formation of the lung. To determine the temporal requirements for FGF signaling during pulmonary morphogenesis, Sprouty-4 (Spry-4), an intracellular FGF receptor antagonist, was expressed in epithelial cells of the fetal lung under control of a doxycycline-inducible system. Severe defects in lobulation and severe lung hypoplasia were observed when Spry-4 was expressed throughout fetal lung development (E6.5-E18.5) or from E6.5 until E13.5. Effects of Spry-4 on branching were substantially reversed by removal of doxycycline from the dam at E12.5, but not at E13.5. In contrast, when initiated late in development (E12.5 to birth), Spry-4 caused less severe pulmonary hypoplasia. Expression of Spry-4 from E16.5 to E18.5 reduced lung growth and resulted in perinatal death due to respiratory failure. Expression of Spry-4 during the saccular and alveolar stages, from E18.5 to postnatal day 21, caused mild emphysema. These findings demonstrate that the embryonic-pseudoglandular stage is a critical time period during which Spry-sensitive pathways are required for branching morphogenesis, lobulation, and formation of the peripheral lung parenchyma. |
