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.
Didier Trono, Jacques Fellay, Priscilla Turelli, Christian Axel Wandall Thorball, Sandra Eloise Kjeldsen, Evaristo Jose Planet Letschert, Julien Léonard Duc, Cyril David Son-Tuyên Pulver, Romain Forey, Bara Khubieh, Alexandre Coudray, Michaël Imbeault, Jonas Caspar De Tribolet-Hardy