|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Department of Molecular Biology and Pharmacology, Washington University Medical School, Campus Box 8103, 660 S. Euclid Avenue, St Louis, MO 63110, USA
*Author for correspondence (e-mail: dornitz{at}pcg.wustl.edu)
Accepted March 14, 2001
Mammalian lung develops as an evagination of ventral gut endoderm into the underlying mesenchyme. Iterative epithelial branching, regulated by the surrounding mesenchyme, generates an elaborate network of airways from the initial lung bud. Fibroblast growth factors (FGFs) often mediate epithelial-mesenchymal interactions and mesenchymal Fgf10 is essential for epithelial branching in the developing lung. However, no FGF has been shown to regulate lung mesenchyme. In embryonic lung, Fgf9 is detected in airway epithelium and visceral pleura at E10.5, but is restricted to the pleura by E12.5. We report that mice homozygous for a targeted disruption of Fgf9 exhibit lung hypoplasia and early postnatal death. Fgf9-/- lungs exhibit reduced mesenchyme and decreased branching of airways, but show significant distal airspace formation and pneumocyte differentiation. Our results suggest that Fgf9 affects lung size by stimulating mesenchymal proliferation. The reduction in the amount of mesenchyme in Fgf9-/- lungs limits expression of mesenchymal Fgf10. We suggest a model whereby FGF9 signaling from the epithelium and reciprocal FGF10 signaling from the mesenchyme coordinately regulate epithelial airway branching and organ size during lung embryogenesis.
Key words: FGF9, FGF, FGF receptor, Lung, Mesenchyme, Mouse, Knockout
This article has been cited by other articles:
|
|
 |
|
  M. J. Geske, X. Zhang, K. K. Patel, D. M. Ornitz, and T. S. Stappenbeck Fgf9 signaling regulates small intestinal elongation and mesenchymal development Development, September 1, 2008; 135(17): 2959 - 2968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rajagopal, T. J. Carroll, J. S. Guseh, S. A. Bores, L. J. Blank, W. J. Anderson, J. Yu, Q. Zhou, A. P. McMahon, and D. A. Melton Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme Development, May 1, 2008; 135(9): 1625 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. D. Klein, D. B. Lyons, G. Balooch, G. W. Marshall, M. A. Basson, M. Peterka, T. Boran, R. Peterkova, and G. R. Martin An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors Development, January 15, 2008; 135(2): 377 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. White, K. J. Lavine, and D. M. Ornitz FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network Development, October 15, 2007; 134(20): 3743 - 3752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Drummond, M. Tellbach, M. Dyson, and J. K. Findlay Fibroblast Growth Factor-9, a Local Regulator of Ovarian Function Endocrinology, August 1, 2007; 148(8): 3711 - 3721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, O. A. Ibrahimi, S. K. Olsen, H. Umemori, M. Mohammadi, and D. M. Ornitz Receptor Specificity of the Fibroblast Growth Factor Family: THE COMPLETE MAMMALIAN FGF FAMILY J. Biol. Chem., June 9, 2006; 281(23): 15694 - 15700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. V. Cardoso and J. Lu Regulation of early lung morphogenesis: questions, facts and controversies Development, May 1, 2006; 133(9): 1611 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. White, J. Xu, Y. Yin, C. Smith, G. Schmid, and D. M. Ornitz FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains Development, April 15, 2006; 133(8): 1507 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, T. S. Stappenbeck, A. C. White, K. J. Lavine, J. I. Gordon, and D. M. Ornitz Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development Development, January 1, 2006; 133(1): 173 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. C. Wing, H.-M. Chen, P.-C. Chuang, M.-H. Wu, and S.-J. Tsai The Mammalian Target of Rapamycin-p70 Ribosomal S6 Kinase but Not Phosphatidylinositol 3-Kinase-Akt Signaling Is Responsible for Fibroblast Growth Factor-9-induced Cell Proliferation J. Biol. Chem., May 20, 2005; 280(20): 19937 - 19947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Chailley-Heu, O. Boucherat, A.-M. Barlier-Mur, and J. R. Bourbon FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L43 - L51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Adam, S. H. Eaton, C. Estrada, A. Nimgaonkar, S.-C. Shih, L. E. H. Smith, I. S. Kohane, D. Bagli, and M. R. Freeman Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells Physiol Genomics, December 15, 2004; 20(1): 36 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Hyatt, X. Shangguan, and J. M. Shannon FGF-10 induces SP-C and Bmp4 and regulates proximal-distal patterning in embryonic tracheal epithelium Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1116 - L1126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Whitsett, S. E. Wert, and B. C. Trapnell Genetic disorders influencing lung formation and function at birth Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R207 - R215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Schmahl, Y. Kim, J. S. Colvin, D. M. Ornitz, and B. Capel Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination Development, August 1, 2004; 131(15): 3627 - 3636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jin, F. Wang, X. Wu, C. Yu, Y. Luo, and W. L. McKeehan Directionally Specific Paracrine Communication Mediated by Epithelial FGF9 to Stromal FGFR3 in Two-Compartment Premalignant Prostate Tumors Cancer Res., July 1, 2004; 64(13): 4555 - 4562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Newman, C.-M. Li, R. Simmons, J. Khosla, and P. L. Sannes Heparin affects signaling pathways stimulated by fibroblast growth factor-1 and -2 in type II cells Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L191 - L200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Land and F. Darakhshan Thymulin evokes IL-6-C/EBP{beta} regenerative repair and TNF-{alpha} silencing during endotoxin exposure in fetal lung explants Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L473 - L487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-Y. C. Wing, P.-C. Chuang, M.-H. Wu, H.-M. Chen, and S.-J. Tsai Expression and Mitogenic Effect of Fibroblast Growth Factor-9 in Human Endometriotic Implant Is Regulated by Aberrant Production of Estrogen J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5547 - 5554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dono Fibroblast growth factors as regulators of central nervous system development and function Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R867 - R881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Sakiyama, A. Yamagishi, and A. Kuroiwa Tbx4-Fgf10 system controls lung bud formation during chicken embryonic development Development, April 1, 2003; 130(7): 1225 - 1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shu, Y. Q. Jiang, M. M. Lu, and E. E. Morrisey Wnt7b regulates mesenchymal proliferation and vascular development in the lung Development, March 12, 2003; 129(20): 4831 - 4842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kratochwil, J. Galceran, S. Tontsch, W. Roth, and R. Grosschedl FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1-/- mice Genes & Dev., December 15, 2002; 16(24): 3173 - 3185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. W. Gonzales, S. H. Guttentag, K. C. Wade, A. D. Postle, and P. L. Ballard Differentiation of human pulmonary type II cells in vitro by glucocorticoid plus cAMP Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L940 - L951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mood, R. Friesel, and I. O. Daar SNT1/FRS2 Mediates Germinal Vesicle Breakdown Induced by an Activated FGF Receptor1 in Xenopus Oocytes J. Biol. Chem., August 30, 2002; 277(36): 33196 - 33204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Tsai, M.-H. Wu, H.-M. Chen, P.-C. Chuang, and L.-Y. C. Wing Fibroblast Growth Factor-9 Is an Endometrial Stromal Growth Factor Endocrinology, July 1, 2002; 143(7): 2715 - 2721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Ornitz and P. J. Marie FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease Genes & Dev., June 15, 2002; 16(12): 1446 - 1465. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Whitsett, J. C. Clark, L. Picard, J. W. Tichelaar, S. E. Wert, N. Itoh, A.-K. T. Perl, and M. T. Stahlman Fibroblast Growth Factor 18 Influences Proximal Programming during Lung Morphogenesis J. Biol. Chem., June 14, 2002; 277(25): 22743 - 22749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Liu, J. Xu, J. S. Colvin, and D. M. Ornitz Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18 Genes & Dev., April 1, 2002; 16(7): 859 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhao, F.-C. Hung, J. S. Colvin, A. White, W. Dai, F. J. Lovicu, D. M. Ornitz, and P. A. Overbeek Patterning the optic neuroepithelium by FGF signaling and Ras activation Development, December 15, 2001; 128(24): 5051 - 5060. [Abstract] [Full Text] [PDF]
|
|
