Development 130, e1205 (2003)
Copyright © 2003 The Company of Biologists Limited
Tbx4 and Tbx5: dual roles in limb development revealed
Three papers in this issue together show, for the first time, that the
T-box transcription factors Tbx4 and Tbx5 have critically important roles in
specifying limb identity and in maintaining limb outgrowth through their
regulation of genes that are essential for limb development. Toshihiko Ogura
and colleagues misexpressed dominant-negative forms of these genes in the
prospective limb fields of chick embryos (see
p. 2729). This
misexpression produced limbless phenotypes, and the repression of the
Wnt2b, Wnt8c, Fgf8 and Fgf10 genes. By contrast, when
Tbx5 and Tbx4 were misexpressed in chick embryo flanks,
additional wing- (in response to Tbx5) and leg-like (in response to
Tbx4) structures were induced, accompanied by the upregulation of
Wnts and Fgfs. Thus, each Tbx gene confers a specific limb identity –
Txb5 the forelimb/wing and Tbx4 the hindlimb – and
initiates limb development by activating a Wnt/Fgf signalling cascade, as also
indicated in the accompanying papers. When Logan and colleagues conditionally
inactivated Tbx5 in the developing mouse forelimb (see
p. 2741), the
forelimb bud completely failed to grow and Fgf10 expression was lost
from the prospective forelimb bud mesenchyme, resulting in extensive
apoptosis. This team also misexpressed dominant-negative and
dominant-activated forms of Tbx5 in the chick wing to reveal that Tbx5 is also
required at later stages of limb bud development for continued limb outgrowth.
By contrast, when Papaioannou and colleagues inactivated Tbx4 in mice
(see p. 2681), the
initial patterning of hindlimb buds occurred normally but hindlimb development
subsequently failed, in vitro and in vivo. Together these findings shed new
light on a conserved genetic network that controls vertebrate limb
development, and on the position and function of these Tbx genes in this
network.
Related articles in Development:
- Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois
- L. A. Naiche and Virginia E. Papaioannou
Development 2003 130: 2681-2693.
[Abstract]
[Full Text]
- Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt/Fgf signaling cascade
- Jun K. Takeuchi, Kazuko Koshiba-Takeuchi, Takayuki Suzuki, Mika Kamimura, Keiko Ogura, and Toshihiko Ogura
Development 2003 130: 2729-2739.
[Abstract]
[Full Text]
- Tbx5 is required for forelimb bud formation and continued outgrowth
- Charalampos Rallis, Benoit G. Bruneau, Jo Del Buono, Christine E. Seidman, J. G. Seidman, Sahar Nissim, Clifford J. Tabin, and Malcolm P. O. Logan
Development 2003 130: 2741-2751.
[Abstract]
[Full Text]
