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Developmental biology

Legs to wings and back again

Nature volume 398, pages 751–752 (1999)Cite this article

How do arms or wings (forelimbs) become different from legs (hindlimbs)? This biological problem has interesting evolutionary implications, and a handful of papers1,2,3,4 — including reports by Takeuchi et al.1 and Rodriguez-Esteban et al.2 on pages 810 and 814 of this issue — provide the first tantalizing molecular clues. They show that two transcription factors, Tbx5 and Tbx4, which are expressed in the developing forelimb and hindlimb, respectively, control the identity of arms and legs.

But why are the limbs not completely transformed when these genes are misexpressed? Perhaps the specification of limb identity relies on a number of events, only a subset of which are affected by the loss or gain of a single transcription factor. Moreover, experimental limitations may reduce the scope of the transformations. The first limitation — timing of misexpression — is critical. Other studies indicate that the identity of fore- and hindlimbs is set early and retained, even if leg tissue is grafted to the wing (resulting in wings with toes and claws) or vice versa5,6. Takeuchi et al.1 used in ovo electroporation, which allows rapid expression of introduced DNA, yet they still found that the transformations were incomplete. The second limitation is continued production of the proteins that are normally expressed in the limbs. For example, when Pitx1 or Tbx4 are misexpressed in the wing, production of Tbx5 persists, and this may maintain wing identity. But when Tbx5 is misexpressed in the leg, expression of Tbx4 drops considerably. Again, transformation is incomplete, perhaps because expression of the upstream ‘leg’ regulator Pitx1 is unaffected.

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Figure 1: Effect of the Tbx and Pitx proteins on fore- and hindlimb identity.

References

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  1. the Department of Molecular Biology, Memorial Sloan Kettering Cancer Center, and the Howard Hughes Medical Institute, 1275 York Avenue, New York, 10021, New York, USA

    Lee Niswander

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  1. Lee Niswander
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Niswander, L. Legs to wings and back again. Nature 398, 751–752 (1999). https://doi.org/10.1038/19625

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