Regulatory constraints in the evolution of the tetrapod limb anterior–posterior polarity
Basile Tarchini, Denis Duboule and Marie Kmita
Nature 443, 985-988 (26 October 2006) | doi:10.1038/nature05247
From the conclusion :
Consequently, we suggest that tetrapod limbs evolved along with the recruitment of the Hox collinear mechanism implemented in the developing body axis. This regulatory co-option imposed collinearity within limb buds, leading to the posterior-only expression of 5′-located Hox genes. Because these latter genes have the capacity to elicit Shh transcription, Shh signalling was confined to posterior limb bud cells, and hence the limb emerged with a built-in A–P polarity. Alternatively, all HOX proteins originally may have had the capacity to regulate Shh, this property being subsequently restricted to some genes only, to generate an A–P polarized structure. However, the absence of animals with appendages showing a truly bilateral symmetry, including ancestral tetrapod fossils, makes the latter scenario unlikely.
In the former view, the limb A–P polarity is a collateral effect of the genetic strategy co-opted for the distal extension of our limbs, a process highly constrained by the intrinsic logic of our body architecture. The necessity of restricting expression of 59-located Hox genes caudally during gastrulation to prevent the deleterious effects of their products if expressed too rostrally in the main body axis (for example, see ref. 24), is thus probably the origin of their posterior expression in limb buds and of the consequent appendage A–P polarity. In this context, rather than the result of the selection of an independent regulatory strategy applied to an appendage because of the obvious adaptative advantages associated with such a polarity, we may consider that this polarity simply reflects the most parsimonious way of producing a limb.
Abstract
The anterior to posterior (A–P) polarity of the tetrapod limb is determined by the confined expression of Sonic hedgehog (Shh) at the posterior margin of developing early limb buds, under the control of HOX proteins encoded by gene members of both the HoxA and HoxD clusters. Here, we use a set of partial deletions to show that only the last four Hox paralogy groups can elicit this response: that is, precisely those genes whose expression is excluded from most anterior limb bud cells owing to their collinear transcriptional activation. We propose that the limb A–P polarity is produced as a collateral effect of Hox gene collinearity, a process highly constrained by its crucial importance during trunk development. In this view, the co-option of the trunk collinear mechanism, along with the emergence of limbs, imposed an A–P polarity to these structures as the most parsimonious solution. This in turn further contributed to stabilize the architecture and operational mode of this genetic system.
