Fig. 4

New alternative evolutionary scenario for the endostyle and thyroid gland. A–D Hypothetical independent evolutionary events that occurred during chordate evolution. Arrows indicate developmental sequence. A Acquisition of the primitive endostyle, which originated from the pharyngeal endoderm with broad expression of Nkx2-1/2-4 and subordinate endostyle GRN. B Thyroid follicles arise from a subset of epithelial cells in the endostyle with the acquisition of thyroid GRN including Nkx2-1/2-4, Pax2/5/8, and Hhex. Co-existence: the primitive endostyle and thyroid follicles are not mutually exclusive in this state. C Anatomy and developmental module of the primitive endostyle was lost in the LCA of modern vertebrates. Crown group of cyclostomes have retained the early and broad expression of Nkx2-1/2-4. C’ According to the classical hypothesis, the independent GRN of the primitive endostyle may have enabled the loss of its morphology without influencing thyroid development in each ancestor of gnathostomes, hagfishes, and possibly stem lampreys. D In the LCA of modern lampreys, an atavistic endostyle is secondarily acquired by recruiting a similar developmental module to form the endostyle. END, endostyle; THY, thyroid