Retinoic acid is a key regulatory switch determining the difference between lung and thyroid fates in Xenopus laevis

If either retinoic acid or Fgf signalling is inhibited, there is no differentiation of the lung as assayed by expression of sftpb. There is no change in expression of thyroid gland markers when retinoic acid signalling is blocked after gastrulation and when Fgf signalling is inhibited there is a short window of time where pax2 expression is inhibited but expression of other markers is unaffected. If exogenous retinoic acid is given to the embryo between embryonic stages 20 and 26, the presumptive thyroid expresses sftpb and sftpc, specific markers of lung differentiation and expression of key thyroid transcription factors is lost. When the presumptive thyroid is transplanted into the posterior embryo, it also expresses sftpb, although pax2 expression is not blocked.After gastrulation, retinoic acid is required for lung but not thyroid differentiation in Xenopus while Fgf signalling is needed for lung but only for early expression of pax2 in the thyroid. Exposure to retinoic acid can cause the presumptive thyroid to switch to a lung developmental program.The differentiation of specific organs from the endoderm is directly related to their position along the anteroposterior axis of the vertebrate embryo. After initial specification of the endoderm, wnt, nodal, bone morphogenetic protein and fibroblast growth factor (Fgf) signals quickly subdivide the gut into the foregut, midgut and hindgut [1]. Expression of hhex, sox2 and foxa2 are associated with the foregut [2] whereas expression of sox17 [3] and cdx [4] genes is eventually restricted to posterior endoderm. The foregut will give rise to the thyroid, thymus, parathyroid, lung, liver, pancreas, and stomach.Although specific transcription factors are associated with each of these organ systems in later development, expression of key transcription factors at early stages is not restricted to a specific organ system. In the foregut, nkx2.1 (or ttf1) is required for development of both the lung and thyroid suggesting a