The fully linked HTML version of this article has now been published.
Development ePress online publication date 24 Aug 2005
doi: 10.1242/dev.02001
Research article
Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning
Jamie M. Verheyden,
Mark Lewandoski,
Chuxia Deng,
Brian D. Harfe,
and
Xin Sun*
* Author for correspondence (e-mail: xsun{at}wisc.edu)
Previous studies have implicated fibroblast growth factor receptor 1 (FGFR1) in limb development. However, the precise nature and complexity of its role have not been defined. Here, we dissect Fgfr1 function in mouse limb by conditional inactivation of Fgfr1 using two different Cre recombinase-expressing lines. Use of the T (brachyury)-cre line led to Fgfr1 inactivation in all limb bud mesenchyme (LBM) cells during limb initiation. This mutant reveals FGFR1 function in two phases of limb development. In a nascent limb bud, FGFR1 promotes the length of the proximodistal (PD) axis while restricting the dimensions of the other two axes. It also serves an unexpected role in limiting LBM cell number in this early phase. Later on during limb outgrowth, FGFR1 is essential for the expansion of skeletal precursor population by maintaining cell survival. Use of mice carrying the sonic hedgehogcre (Shhcre) allele led to Fgfr1 inactivation in posterior LBM cells. This mutant allows us to test the role of Fgfr1 in gene expression regulation without disturbing limb bud growth. Our data show that during autopod patterning, FGFR1 influences digit number and identity, probably through cell-autonomous regulation of Shh expression. Our study of these two Fgfr1 conditional mutants has elucidated the multiple roles of FGFR1 in limb bud establishment, growth and patterning.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Hernandez-Martinez, S. Castro-Obregon, and L. Covarrubias
Progressive interdigital cell death: regulation by the antagonistic interaction between fibroblast growth factor 8 and retinoic acid
Development,
November 1, 2009;
136(21):
3669 - 3678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Tzchori, T. F. Day, P. J. Carolan, Y. Zhao, C. A. Wassif, L. Li, M. Lewandoski, M. Gorivodsky, P. E. Love, F. D. Porter, et al.
LIM homeobox transcription factors integrate signaling events that control three-dimensional limb patterning and growth
Development,
April 15, 2009;
136(8):
1375 - 1385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Burtscher and H. Lickert
Foxa2 regulates polarity and epithelialization in the endoderm germ layer of the mouse embryo
Development,
March 15, 2009;
136(6):
1029 - 1038.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
K. Yu and D. M. Ornitz
FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis
Development,
February 1, 2008;
135(3):
483 - 491.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Wahl, C. Deng, M. Lewandoski, and O. Pourquie
FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis
Development,
November 15, 2007;
134(22):
4033 - 4041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Naiche and V. E. Papaioannou
Tbx4 is not required for hindlimb identity or post-bud hindlimb outgrowth
Development,
January 1, 2007;
134(1):
93 - 103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Li, X. Xu, D. K. Nelson, T. Williams, M. R. Kuehn, and C.-X. Deng
FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis
Development,
November 1, 2005;
132(21):
4755 - 4764.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
