QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 19 September 2007
doi: 10.1242/dev.004879

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.004879v1 134/20/3743    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by White, A. C. Articles by Ornitz, D. M. Search for Related Content PubMed PubMed Citation Articles by White, A. C. Articles by Ornitz, D. M. Social Bookmarking                         What's this?

FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA.

^* Author for correspondence (e-mail: dornitz{at}wustl.edu)

Accepted 27 July 2007

The juxtaposition of a dense capillary network to lung epithelial cells is essential for air-blood gas exchange. Defective lung vascular development can result in bronchopulmonary dysplasia and alveolar capillary dysplasia. Although vascular endothelial growth factor A (Vegfa) is required for formation of the lung capillary network, little is known regarding the factors that regulate the density and location of the distal capillary plexus and the expression pattern of Vegfa. Here, we show that fibroblast growth factor 9 (FGF9) and sonic hedgehog (SHH) signaling to lung mesenchyme, but not to endothelial cells, are each necessary and together sufficient for distal capillary development. Furthermore, both gain- and loss-of-function of FGF9 regulates Vegfa expression in lung mesenchyme, and VEGF signaling is required for FGF9-mediated blood vessel formation. FGF9, however, can only partially rescue the reduction in capillary density found in the absence of SHH signaling, and SHH is unable to rescue the vascular phenotype found in Fgf9^-/- lungs. Thus, both signaling systems regulate distinct aspects of vascular development in distal lung mesenchyme. These data suggest a molecular mechanism through which FGF9 and SHH signaling coordinately control the growth and patterning of the lung capillary plexus, and regulate the temporal and spatial expression of Vegfa.

Key words: Fibroblast growth factor 9 (FGF9), Vascular endothelial growth factor (VEGF), Sonic hedgehog (SHH), Lung development, Angiogenesis, Mesenchyme, Mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. R. Swift and B. M. Weinstein Arterial-Venous Specification During Development Circ. Res., March 13, 2009; 104(5): 576 - 588. [Abstract] [Full Text] [PDF]

				M. A. Schwarz, L. Caldwell, D. Cafasso, and H. Zheng Emerging pulmonary vasculature lacks fate specification Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L71 - L81. [Abstract] [Full Text] [PDF]

				J. Que, B. Wilm, H. Hasegawa, F. Wang, D. Bader, and B. L. M. Hogan Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development PNAS, October 28, 2008; 105(43): 16626 - 16630. [Abstract] [Full Text] [PDF]

				M. Varjosalo and J. Taipale Hedgehog: functions and mechanisms Genes & Dev., September 15, 2008; 22(18): 2454 - 2472. [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]

				M. Loscertales, A. J. Mikels, J. K.-H. Hu, P. K. Donahoe, and D. J. Roberts Chick pulmonary Wnt5a directs airway and vascular tubulogenesis Development, April 1, 2008; 135(7): 1365 - 1376. [Abstract] [Full Text] [PDF]