Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds

Abstract

Much progress has been made in understanding limb development. Most genes are expressed equally and in the same pattern in the fore- and hindlimbs, which nevertheless develop into distinct structures. The T-box genes Tbx5 and Tbx4, on the other hand, are expressed differently in chick wing (Tbx5) and leg (Tbx4) buds. Molecular analysis of the optomotor blind gene, which belongs to the same family of transcription factors, has revealed that this gene is involved in the transdetermination of Drosophila wing and leg imaginal discs. In addition, expression of Tbx5 and Tbx4 correlates well with the identity of ectopic limb buds induced by fibroblast growth factor. Thus, it is thought that Tbx5 and Tbx4 might be involved in determining limb identity. Another candidate is the Pitx1 gene, which encodes a bicoid-type homeodomain transcription factor that is expressed in leg buds. Here we determine the importance of these factors in establishing limb identity.

The human TBX5 gene mutation database

“…The Exons 2 -9 range from 92 to 575 bp and code for a protein containing 518 amino acids. The TBX5 protein is principally expressed in the developing forelimb and heart related vascular bed, but also within the developing neural retina (Basson et al, 1997;Li et al, 1997;Rodriguez-Esteban et al, 1999;Takeuchi et al, 1999;Sowden et al, 2001). On site it acts as an indispensable element in a transcriptional regulatory cascade during forelimb-and cardiogenesis.…”

Finger or toe: the molecular basis of limb identity

“…Ectopic expression of Tbx5 in the developing chick hindlimb bud can, at least partially, transform the identity of the leg to a more wing-like morphology Takeuchi et al, 1999). In the limb bud, ectopically expressed Tbx5 can induce the expression of forelimb markers, such as Hoxd9, and repress the expression of hindlimb markers, for example Hoxc9.…”

“…If allowed to develop to later stages, the resulting limbs produce elements with morphological characteristics of a wing, such as wing digits and feather buds. In the converse experiment, hindlimb-specific genes Tbx4 or Pitx1 misexpressed in the forelimb can transform the wing to a more hindlimb character (Logan and Tabin, 1999;Takeuchi et al, 1999). Similarly, Tbx4 can transform the identity of Fgf-induced ectopic limbs induced in the interlimb region of the LPM (RodriguezEsteban et al, 1999;Takeuchi et al, 1999).…”

“…In the converse experiment, hindlimb-specific genes Tbx4 or Pitx1 misexpressed in the forelimb can transform the wing to a more hindlimb character (Logan and Tabin, 1999;Takeuchi et al, 1999). Similarly, Tbx4 can transform the identity of Fgf-induced ectopic limbs induced in the interlimb region of the LPM (RodriguezEsteban et al, 1999;Takeuchi et al, 1999). Again, genes that are normally restricted to the hindlimb, such as Hoxc10 and Hoxc11, are ectopically induced in the targeted forelimb or ectopic limb and, if these limbs are allowed to develop further, they produce characteristic leg-like elements such as clawed toes and scales.…”

“…This can be explained in part by the observation that, following the misexpression of Tbx4 or Pitx1, the endogenous expression of Tbx5 in the forelimb is unchanged (Logan and Tabin, 1999;Rodriguez-Esteban et al, 1999;Takeuchi et al, 1999). This observation indicates that in these misexpression experiments, cells in the limb are presented with two competing programmes; in some cases one programme may dominate, whereas in others the cells may assume a mixed or intermediate fate.…”