Indeed, the hallmark of the huntingtin deficient molecular phenotype is the impaired down-regulation of a subset of dynamically expressed genes, after the proper onset of expression. This phenomenon does not reflect a lack of anterior/posterior axis formation, as evidenced by the formation of the AVE anteriorly and the primitive streak posteriorly. Nor can it be simply explained by delayed development, as stage-specific markers, such as Wnt3a and primordial germ cells, which are detectable at E7.0 in wild-type embryos, are induced appropriately. Furthermore, the expression of T and Evx1 in the extraembryonic mesoderm of mutant embryos is not a feature of wild-type embryos, even at earlier stages. This strongly suggests that in huntingtin deficient embryos, the migration of the distal streak derivatives to the extraembryonic mesoderm occurs normally but that the down-regulation of these genes is impaired. This impairment may also explain the failure of huntingtin deficient embryos to properly restrict the expression of Fgf8, Nodal and Gsc. Thus, huntingtin may play a direct role in the transcriptional regulation, or mRNA stability of these genes or it may act indirectly by intersecting with other pathways that regulate the expression of these genes.