|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
1 Departamento de Ciencias Morfológicas y Biología Celular y Animal, Universidad de Extremadura, Badajoz 06071, Spain
2 Instituto Gulbenkian de Ciência, Rue da Quinta Grande, 6 Oeiras, Portugal
3 Department of Anatomy and Physiology, The Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK
4 Unidad de Investigación, Hospital Marques de Valdecilla, Santander 39008, Spain
5 Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Cantabria, Santander 39011, Spain
6 Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain
*Author for correspondence (e-mail: hurlej{at}unican.es)
Accepted March 29, 2001
We have investigated the role of FGFs in the control of programmed cell death during limb development by analyzing the effects of increasing and blocking FGF signaling in the avian limb bud. BMPs are currently considered as the signals responsible for cell death. Here we show that FGF signaling is also necessary for apoptosis and that the establishment of the areas of cell death is regulated by the convergence of FGF- and BMP-mediated signaling pathways. As previously demonstrated, cell death is inhibited for short intervals (12 hours) after administration of FGFs. However, this initial inhibition is followed (24 hours) by a dramatic increase in cell death, which can be abolished by treatments with a BMP antagonist (Noggin or Gremlin). Conversely, blockage of FGF signaling by applying a specific FGF-inhibitor (SU5402) into the interdigital regions inhibits both physiological cell death and that mediated by exogenous BMPs. Furthermore, FGF receptors 1, 2 and 3 are expressed in the autopodial mesoderm during the regression of the interdigital tissue, and the expression of FGFR3 in the interdigital regions is regulated by FGFs and BMPs in the same fashion as apopotosis. Together our findings indicate that, in the absence of FGF signaling BMPs are not sufficient to trigger apoptosis in the developing limb. Although we provide evidence for a positive influence of FGFs on BMP gene expression, the physiological implication of FGFs in apoptosis appears to result from their requirement for the expression of genes of the apoptotic cascade. We have identified MSX2 and Snail as candidate genes associated with apoptosis the expression of which requires the combined action of FGFs and BMPs.
Key words: Apoptosis, BMP, FGF receptors, Snail, MSX2, Syndactyly, Chick, Duck
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Higgins, S. H. X. Wong, M. Richner, C. L. Rowe, D. F. Newgreen, G. A. Werther, and V. C. Russo Fibroblast Growth Factor 2 Reactivates G1 Checkpoint in SK-N-MC Cells via Regulation of p21, Inhibitor of Differentiation Genes (Id1-3), and Epithelium-Mesenchyme Transition-Like Events Endocrinology, September 1, 2009; 150(9): 4044 - 4055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pajni-Underwood, C. P. Wilson, C. Elder, Y. Mishina, and M. Lewandoski BMP signals control limb bud interdigital programmed cell death by regulating FGF signaling Development, June 15, 2007; 134(12): 2359 - 2368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Arnaud-Dabernat, M. Kritzik, A. G. Kayali, Y.-Q. Zhang, G. Liu, C. Ungles, and N. Sarvetnick FGFR3 Is a Negative Regulator of the Expansion of Pancreatic Epithelial Cells Diabetes, January 1, 2007; 56(1): 96 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Ali-Khan and B. F. Hales Novel Retinoid Targets in the Mouse Limb during Organogenesis Toxicol. Sci., November 1, 2006; 94(1): 139 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Weatherbee, R. R. Behringer, J. J. Rasweiler IV, and L. A. Niswander Interdigital webbing retention in bat wings illustrates genetic changes underlying amniote limb diversification PNAS, October 10, 2006; 103(41): 15103 - 15107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Panman, A. Galli, N. Lagarde, O. Michos, G. Soete, A. Zuniga, and R. Zeller Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling Development, September 1, 2006; 133(17): 3419 - 3428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lu, G. Minowada, and G. R. Martin Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function Development, January 1, 2006; 133(1): 33 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishii, J. Han, H.-Y. Yen, H. M. Sucov, Y. Chai, and R. E. Maxson Jr Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest Development, November 15, 2005; 132(22): 4937 - 4950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Bryant, F. G. Wylie, and J. L. Stow Regulation of Endocytosis, Nuclear Translocation, and Signaling of Fibroblast Growth Factor Receptor 1 by E-Cadherin Mol. Biol. Cell, January 1, 2005; 16(1): 14 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Chung, J. Hyodo-Miura, A. Kitayama, C. Terasaka, T. Nagamune, and N. Ueno Screening of FGF target genes in Xenopus by microarray: temporal dissection of the signalling pathway using a chemical inhibitor Genes Cells, August 1, 2004; 9(8): 749 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Dao, A. Y. Shin, A. Billings, K. C. Oberg, and V. E. Wood Surgical Treatment of Congenital Syndactyly of the Hand J. Am. Acad. Ortho. Surg., January 1, 2004; 12(1): 39 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, C. Liu, Y. Yamada, and C.-M. Fan growth arrest specific gene 1 acts as a region-specific mediator of the Fgf10/Fgf8 regulatory loop in the limb Development, March 13, 2003; 129(22): 5289 - 5300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ashique, K. Fu, and J. M. Richman Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival during avian lip fusion Development, January 10, 2002; 129(19): 4647 - 4660. [Abstract] [Full Text] [PDF]
|
|
