Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung
- PMID:15305287
- DOI: 10.1002/dvdy.20105
Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung
Abstract
Sonic hedgehog (Shh) was conditionally deleted in respiratory epithelial cells of the embryonic lung in vivo. Deletion of Shh before embryonic day (E) 13.5 resulted in respiratory failure at birth. While lobulation was not perturbed, the lungs were hypoplastic, with reduced branching of peripheral lung tubules, evident from E13.5. Smooth muscle and endothelial cells were absent or reduced, the latter in relationship to the loss of peripheral lung parenchyma. Tracheal-bronchial ring abnormalities occurred when Shh was deleted between E8.5 and E12.5. Deletion of Shh later in gestation (after E13.5) caused mild abrogation of peripheral branching morphogenesis but did not disrupt tracheal-bronchial development. Defects in branching morphogenesis and vascularization seen in Shh null mutant (Shh(-/-)) mice were substantially corrected when SHH was ectopically expressed in the respiratory epithelium; however, peripheral expression of SHH failed to correct cartilage abnormalities in the trachea and bronchi, indicating a spatial requirement for SHH expression near sites of cartilage formation. Expression of SHH by the respiratory epithelium plays an important role in the patterning of tracheal-bronchial mesenchyme required for formation of cartilage rings in conducting airways. SHH regulates branching morphogenesis and influences differentiation of the peripheral lung mesenchyme required for formation of bronchial and vascular smooth muscle.
Similar articles
- Induction of bud formation of embryonic mouse tracheal epithelium by fibroblast growth factor plus transferrin in mesenchyme-free culture.Ohtsuka N, Urase K, Momoi T, Nogawa H.Ohtsuka N, et al.Dev Dyn. 2001 Oct;222(2):263-72. doi: 10.1002/dvdy.1206.Dev Dyn. 2001.PMID:11668603
- Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis.Li Y, Zhang H, Choi SC, Litingtung Y, Chiang C.Li Y, et al.Dev Biol. 2004 Jun 1;270(1):214-31. doi: 10.1016/j.ydbio.2004.03.009.Dev Biol. 2004.PMID:15136151
- Defective sonic hedgehog signaling in esophageal atresia with tracheoesophageal fistula.Spilde TL, Bhatia AM, Mehta S, Ostlie DJ, Hembree MJ, Preuett BL, Prasadan K, Li Z, Snyder CL, Gittes GK.Spilde TL, et al.Surgery. 2003 Aug;134(2):345-50. doi: 10.1067/msy.2003.243.Surgery. 2003.PMID:12947339
- Sonic hedgehog regulates branching morphogenesis in the mammalian lung.Pepicelli CV, Lewis PM, McMahon AP.Pepicelli CV, et al.Curr Biol. 1998 Sep 24;8(19):1083-6. doi: 10.1016/s0960-9822(98)70446-4.Curr Biol. 1998.PMID:9768363Review.
- Regulation of early lung morphogenesis: questions, facts and controversies.Cardoso WV, Lü J.Cardoso WV, et al.Development. 2006 May;133(9):1611-24. doi: 10.1242/dev.02310.Development. 2006.PMID:16613830Review.
Cited by
- Bifurcating action of Smoothened in Hedgehog signaling is mediated by Dlg5.Chong YC, Mann RK, Zhao C, Kato M, Beachy PA.Chong YC, et al.Genes Dev. 2015 Feb 1;29(3):262-76. doi: 10.1101/gad.252676.114.Genes Dev. 2015.PMID:25644602Free PMC article.
- Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria.Zacharias WJ, Li X, Madison BB, Kretovich K, Kao JY, Merchant JL, Gumucio DL.Zacharias WJ, et al.Gastroenterology. 2010 Jun;138(7):2368-77, 2377.e1-4. doi: 10.1053/j.gastro.2010.02.057. Epub 2010 Mar 3.Gastroenterology. 2010.PMID:20206176Free PMC article.
- Fibroblast growth factor 18 gives growth and directional cues to airway cartilage.Elluru RG, Thompson F, Reece A.Elluru RG, et al.Laryngoscope. 2009 Jun;119(6):1153-65. doi: 10.1002/lary.20157.Laryngoscope. 2009.PMID:19358209Free PMC article.
- Evolution of Shh endoderm enhancers during morphological transition from ventral lungs to dorsal gas bladder.Sagai T, Amano T, Maeno A, Kimura T, Nakamoto M, Takehana Y, Naruse K, Okada N, Kiyonari H, Shiroishi T.Sagai T, et al.Nat Commun. 2017 Feb 3;8:14300. doi: 10.1038/ncomms14300.Nat Commun. 2017.PMID:28155855Free PMC article.
- Osr1 functions downstream of Hedgehog pathway to regulate foregut development.Han L, Xu J, Grigg E, Slack M, Chaturvedi P, Jiang R, Zorn AM.Han L, et al.Dev Biol. 2017 Jul 1;427(1):72-83. doi: 10.1016/j.ydbio.2017.05.005. Epub 2017 May 10.Dev Biol. 2017.PMID:28501478Free PMC article.
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases