HMGA2 is required in the neural crest cells of Xenopus laevis

HMGA proteins are small DNA binding proteins that use conserved “AT-hook” motifs to interact with DNA to modify chromatin architecture and assist in gene expression. Two HMGAs, HMGA1 and HMGA2, have been described in mammals, encoded by separate genes. These genes are highly expressed in proliferating and undifferentiated tissues during embryogenesis, but not in adult tissues, where they are re-activated in tumor progression. In Xenopus, only the hmga2 (Xhmga2) gene is described and localized transcripts are first detected at neurula stages, in the presumptive central nervous system (CNS) and eye field, as well as in the neural crest cell (NCC) presumptive territory. At later stages, Xhmga2 mRNA is detected in the CNS, in the otic vesicles, in migrating neural crest cells and their derivatives, in the notochord and in the medio-lateral mesoderm. We are currently addressing the possible role of Xhmga2 in NCCs. We have injected two different morpholinos targeting Xhmga2 transcripts in the anterior neural region and observede that injected embryos have a severe disruption of the branchial arches, that are missing or greatly altered. Analysis of NCC molecular markers show severe downregulation or absence of Xtwist, and Xdll4 expression at the tailbud stage. Extensive cell death occurs in the regions normally occupied by NCC injected embryos. Injection of control mismatched or standard morpholinos did not lead to similar alterations. These data suggest that Xhmga2 is required for NCC survival, possibly during the epithelial-mesenchymal transition and or migratory phase of NCC towards the branchial pouches.