Formation of axial mesoderm

All these cells initially form a single columnar epithelium, the notochordal plate, that is contiguous with the endoderm. The notochordal plate then submerges into the embryo to form the tubular notochord structure. During embryogenesis the notochord not only provides physical stiffness but also produces signaling molecules such as Sonic Hedgehog (SHH) that pattern surrounding tissues. After the notochord forms, it regresses in regions where vertebrae form and expands in the perichordal disc to form the nuclei pulposi, cartilage-like discs that are interspersed with the vertebrae (reviewed in Williams et al. 2019).

Formation of the axial mesoderm is initiated by NODAL signaling via SMAD2,3 proteins that interact with the FOXH1 pioneer transcription factor (inferred from the activities of mouse homologs, as described by Hoodless et al. 2001, Yamamoto et al. 2001). TEAD proteins (inferred from mouse homologs as described by Sawada et al. 2005), which are negatively regulated by the HIPPO signaling pathway, and TBXT (T, BRACHURY) (inferred from mouse homologs, as described by Lolas et al. 2014), whose expression is initiated prior to primitive streak formation, act with the SMADs and FOXH1 to activate FOXA2, which then participates in activating downstream targets such as NOTO and SHH.