spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 24 November 2005
doi: 10.1242/dev.02172

Development 133, 33-42 (2006)
Published by The Company of Biologists 2006
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.02172v1
133/1/33    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lu, P.
Right arrow Articles by Martin, G. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lu, P.
Right arrow Articles by Martin, G. R.

Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function

Pengfei Lu1, George Minowada1,2,* and Gail R. Martin1,{dagger}

1 Department of Anatomy and Program in Developmental Biology, School of Medicinè University of California at San Francisco San Francisco, CA 94143-2711, USA.
2 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Case Western Reserve University, School of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106, USA.

{dagger} Author for correspondence (e-mail: gmartin{at}itsa.ucsf.edu)

Accepted 27 October 2005

A major function of the limb bud apical ectodermal ridge (AER) is to produce fibroblast growth factors (FGFs) that signal to the underlying mesenchyme. Previous studies have suggested that of the four FGF genes specifically expressed in the mouse AER, Fgf8 is unique not only in its expression pattern, but also because it is the only such FGF gene that causes limb skeletal abnormalities when individually inactivated. However, when both Fgf8 and Fgf4 are simultaneously inactivated in the AER, the limb does not develop. One possible explanation for these observations is that although both of these FGF family members contribute to limb development, Fgf8 has functions that Fgf4 cannot perform. To test this hypothesis, we used a novel method to substitute Fgf4 for Fgf8 expression in the developing limb bud by concomitantly activating a conditional Fgf4 gain-of-function allele and inactivating an Fgf8 loss-of-function allele in the same cells via Cre-mediated recombination. Our data show that when Fgf4 is expressed in place of Fgf8, all of the skeletal defects caused by inactivation of Fgf8 are rescued, conclusively demonstrating that FGF4 can functionally replace FGF8 in limb skeletal development. We also show that the increase in FGF signaling that occurs when the Fgf4 gain-of-function allele is activated in a wild-type limb bud causes formation of a supernumerary posterior digit (postaxial polydactyly), as well as cutaneous syndactyly between all the digits. These data underscore the importance of controlling the level of FGF gene expression for normal limb development.

Key words: Cutaneous syndactyly, FGF signaling, Limb development, Apical ectodermal ridge, SHH/FGF loop, Interdigital programmed cell death, Polydactyly, Mouse




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
K. Ellwanger, H. Saito, P. Clement-Lacroix, N. Maltry, J. Niedermeyer, W. K. Lee, R. Baron, G. Rawadi, H. Westphal, and C. Niehrs
Targeted Disruption of the Wnt Regulator Kremen Induces Limb Defects and High Bone Density
Mol. Cell. Biol., August 1, 2008; 28(15): 4875 - 4882.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
P. Lu, Y. Yu, Y. Perdue, and Z. Werb
The apical ectodermal ridge is a timer for generating distal limb progenitors
Development, April 15, 2008; 135(8): 1395 - 1405.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. A. Basson, D. Echevarria, C. Petersen Ahn, A. Sudarov, A. L. Joyner, I. J. Mason, S. Martinez, and G. R. Martin
Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development
Development, March 1, 2008; 135(5): 889 - 898.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
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]

Home page
 DevelopmentHome page
S. Ota, Z.-Q. Zhou, D. R. Keene, P. Knoepfler, and P. J. Hurlin
Activities of N-Myc in the developing limb link control of skeletal size with digit separation
Development, April 15, 2007; 134(8): 1583 - 1592.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 DevelopmentHome page
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]


© The Company of Biologists Ltd 2006