Making A Hand Or A Foot? Tbx-4 And Tbx-5 Are Involved In Determination Of Fore- And Hindlimb Identity

The development of limb structures is regulated by molecular signalling cascades, some of which have been well defined to date. Similar signalling pathways are involved in outgrowth and patterning in both the fore- and hindlimbs. However, in the chick fore- and hindlimbs are also characterised by marked morphological differences. For example, while the forelimb (wing) develops three digits and is completely covered by feathers, the hindlimb (leg) develops 4 digits and is covered by scales and tuberculae.

Members of the T-box family have been identified in a variety of invertebrates and vertebrates, including humans. These genes encode transcription factors which are involved in regulation of gene transcription.

Tbx4 and Tbx5 genes are specifically expressed in the leg bud and wing bud respectively. Previous studies correlated these genes with specification of limb type identity. Toshihiko Ogura, Jun Takeuchi and coworkers (Nara Institute of Science and Technologie, Nara, Japan) in collaboration with Astrid Vogel-Höpker (Max Planck Institute for Brain Research, Frankfurt/Main, Germany, a recipient of a Japan Promotion of Science Fellowship ) have now shown that misexpression of Tbx4, a hindlimb specific gene, in the presumptive forelimb region of the chick embryo, induced the development of a leg-like structure at the position, where normally a forelimb would develop. The corresponding result, induction of forelimb-like structures in the hindlimb region was observed when the forelimb-specific gene Tbx5, was misexpressed in that region. The phenotypes of these misexpression studies were apparant both morphologically and on the basis of limb-specific expression of molecular markers (e.g. Hox genes). For example, misexpression of Tbx4 in the presumptive forelimb region induced the expression of hindlimb specific genes. In some cases Takeuchi et al could also induce the development of 4 digits and scale formation which are features characteristic f

Contact: Astrid Vogel-Höpker

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