scholarly journals Discordant roles for FGF ligands in lung branching morphogenesis between human and mouse

Author(s):  
Soula Danopoulos ◽  
Matthew E Thornton ◽  
Brendan H Grubbs ◽  
Mark R Frey ◽  
David Warburton ◽  
...  



1996 ◽  
Vol 180 (1) ◽  
pp. 242-257 ◽  
Author(s):  
Jingsong Zhao ◽  
Ding Bu ◽  
Matt Lee ◽  
Harold C. Slavkin ◽  
Frederick L. Hall ◽  
...  


1997 ◽  
Vol 186 (2) ◽  
pp. 224-236 ◽  
Author(s):  
Päivi J. Miettinen ◽  
David Warburton ◽  
Ding Bu ◽  
Jing-Song Zhao ◽  
Joel E. Berger ◽  
...  


2015 ◽  
Vol 157 (3) ◽  
pp. 121-127 ◽  
Author(s):  
T. Miura


Development ◽  
2013 ◽  
Vol 140 (18) ◽  
pp. 3731-3742 ◽  
Author(s):  
T. Volckaert ◽  
A. Campbell ◽  
E. Dill ◽  
C. Li ◽  
P. Minoo ◽  
...  


Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2559-2567 ◽  
Author(s):  
P. Souza ◽  
M. Kuliszewski ◽  
J. Wang ◽  
I. Tseu ◽  
A.K. Tanswell ◽  
...  

The biological role of platelet-derived growth factor (PDGF)-AA in lung morphogenesis was investigated by incubating embryonic lung explants with phosphorothioate antisense PDGF-A oligonucleotides, which decreased PDGF-AA but not PDGF-BB protein content. Antisense PDGF-A oligonucleotides inhibited DNA synthesis. This inhibitory effect of antisense PDGF-A was reversed by the addition of exogenous PDGF-AA but not PDGF-BB. Morphometric analyses of antisense-treated cultures showed a significant reduction in lung size. The number of terminal buds of the lung explants was significantly decreased by antisense PDGF-A oligonucleotides. PDGF-AA but not PDGF-BB attenuated the inhibitory effect of antisense PDGF-A on early lung branching. Sense PDGF-A had no effect on DNA synthesis and early lung branching. Reverse transcriptase-polymerase chain reaction analysis revealed PDGF-A mRNA expression in the epithelial component of the embryonic lung, while message for PDGF alpha-receptor was expressed in the mesenchyme. Incubation of explants with neutralizing PDGF-AA antibodies also reduced DNA synthesis and early branching morphogenesis. We conclude that PDGF-AA and its receptor represent an important epithelial-mesenchymal interaction which plays a critical role in early lung branching morphogenesis.



Author(s):  
Sarah A. Gebb ◽  
Peter Lloyd Jones


2005 ◽  
Vol 282 (2) ◽  
pp. 422-431 ◽  
Author(s):  
Denise Tefft ◽  
Stijn P. De Langhe ◽  
Pierre-Marie Del Moral ◽  
Frederic Sala ◽  
Wei Shi ◽  
...  


2016 ◽  
Vol 311 (6) ◽  
pp. L1036-L1049 ◽  
Author(s):  
Soula Danopoulos ◽  
Michael Krainock ◽  
Omar Toubat ◽  
Matthew Thornton ◽  
Brendan Grubbs ◽  
...  

Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation.



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