The requirement for huntingtin in the extraembryonic tissues had prompted us to test whether impaired extraembryonic signals might be responsible for the dysregulation of gene expression within the epiblast that is observed in Hdhex4/5/Hdhex4/5 embryos. Extraembryonic development in Hdhex4/5/Hdhex4/5 embryos is associated with mildly elevated levels expression of Hnf4 in the primitive endoderm and Pem in the lopsided anterior chorion but the expression of other known signals, such as Bmp4 from the extraembryonic ectoderm, and Dkk1 and Lefty1 from the AVE, appear to be normal, although the slight increase in Dkk-1 expression in Hdhex4/5/Hdhex4/5 embryos suggests that further investigation into Wnt signaling is warranted. Moreover, extraembryonic Bmp4 signaling is not impaired in the absence of huntingtin, as the induction of PCGs in mutant embryos is normal, implying proper transport and secretion of the appropriate extraembryonic signals. However, Nodal, Fgf8 and Gsc are expressed ectopically in the visceral endoderm of Hdhex4/5/Hdhex4/5 embryos. Both Nodal and Fgf8, important growth factors required for normal development of the epiblast, are tightly regulated during gastrulation. Therefore, misexpression of either or both of these factors, or of goosecoid, in the visceral endoderm could contribute to the Hdhex4/5/Hdhex4/5 mutant phenotype. In addition, it is possible that other extraembryonic signal(s) that we have not analyzed may also be affected by the lack of huntingtin activity in extraembryonic cells in mutant embryos.