15-P016 Evolution of HoxA genes towards extra-embryonic functions

Hox genes are well known for their key contribution to the establishment of the body architecture. This function relies on both local and long-range cis-regulatory elements that generate nested expression patterns of the various Hox genes along the anterior–posterior axis of the developing embryo. Interestingly, analyses of expression patterns in different species suggested that modulation of the transcriptional control of Hox genes is one of the mechanisms underlying morphological evolution. Most Vertebrates have 39 Hox genes organized in four clusters, referred to as HoxA, HoxB, HoxC and HoxD. In contrast to the other Hox clusters, deletion of the HoxA cluster is embryonic lethal at mid-gestation. We found that this phenotype is due to placental defects. Our analyses revealed that the combined loss of function of Hoxa10, Hoxa11 and Hoxa13 impairs de novo vasculogenesis in the allantois, from which the allantoic/umbilical cord vasculature and the endothelium of the placental labyrinth originate. Interestingly, in mice, this function is associated with precocious activation of Hoxa10, Hoxa11 and Hoxa13 at the vicinity of the posterior primitive streak, indicating that the functional recruitment of Hoxa genes in the allantois disrupted the ancestral temporal sequence of Hox gene activation. Analysis of HoxA transcriptional regulation suggests that emergence of an additional cis-regulatory module underlies this particular modification of HoxA transcriptional control. Based on our data, we propose that the evolution of Hoxa genes towards extra-embryonic function contributed to adaptative changes associated with the transition from aquatic to terrestrial life.