Vertebral malformations induced by sodium salicylate correlate with shifts in expression domains of Hox genes.

Wéry, Nathalie Foulon, Olivier Blacker, Ann Picard, Jacques [UCL] Gofflot, Françoise [UCL]

Several embryotoxic agents, which includes sodium salicylate, were reported to induce vertebral variations in the form of supernumerary ribs (SNR) when administered to pregnant rodents. Because the biological significance of SNR in toxicological studies is still a matter of debate, we investigated the molecular basis of this defect by analyzing the possible involvement of Hox genes, known to specify vertebrae identity. Sodium salicylate (300mg/kg) was administered to pregnant rats on gestational day 9 (GD 9). On GD 13, the expression of several Hox genes, selected according to the position of their anterior limit of expression, namely upstream (Hoxa9), at the level (Hoxa10) and downstream (Hoxd9) to the morphological alteration, were analyzed. Posterior shifts in the anterior limit of expression of Hoxa10 and Hoxd9 were observed following exposure to salicylate, which could explain an effect at the level of the axial skeleton. This finding suggests that the appearance of ectopic ribs can be attributed to an anterior transformation of lumbar vertebrae identity into thoracic vertebrae identity. Whether this transformation occurs with all compounds inducing SNR in rats remains to be determined.