Secondary neurulation-fated cells in the tail bud undergo self-renewal and tubulogenesis regulated by a Sox2 gradient

During amniote development, anterior and posterior components of the neural tube form by primary neurulation (PN) and secondary neurulation (SN), respectively. Unlike PN, SN proceeds by the mesenchymal-to-epithelial transition of SN precursors in the tail bud, a critical structure for the axial elongation. Our direct cell labeling delineates non-overlapping territories of SN- and mesodermal precursors in the chicken tail bud. SN-fated precursors are further divided into self-renewing and differentiating cells, a decision regulated by graded expression levels of Sox2. Whereas Sox2 is confined to SN precursors, Brachyury (T) is widely and uniformly distributed in the tail bud, indicating that Sox2+/Brachyury+ cells are neural-fated and not mesodermal. These results uncover multiple steps during the neural posterior elongation, including precocious segregation of SN precursors, their self-renewal, and regulation by graded Sox 2.