Formation of axial mesoderm

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Homo sapiens
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Axial mesoderm, also called chordamesoderm, is formed by cells ingressing at the anterior end of the primitive streak. The axial mesoderm produces three types of cells, namely (from anterior to posterior) prechordal plate, anterior head process, and node-derived notochord precursors (reviewed in Balmer et al. 2016). In mouse and rat, the prechordal plate gives rise to cells in the foregut endoderm, oral endoderm, and ventral cranial mesoderm (Aoto et al. 2009); the anterior head process gives rise to the anterior portion of the notochord; notochord precursors give rise to the remaining posterior region of the notochord. Contribution of axial mesoderm in humans is less well characterized (Muller and O'Rahilly 2003). (
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.
Literature References
PubMed ID Title Journal Year
16207754 Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor

Sasaki, H, Nishizaki, Y, Nishioka, N, Sawada, A, Kondoh, H, Nakayama, R, Yamamoto, S, Yada, Y, Sato, H

Development 2005
12566624 The prechordal plate, the rostral end of the notochord and nearby median features in staged human embryos

Müller, F, O'Rahilly, R

Cells Tissues Organs 2003
30902259 Development of the axial skeleton and intervertebral disc

Williams, S, Alkhatib, B, Serra, R

Curr Top Dev Biol 2019
24616493 Charting Brachyury-mediated developmental pathways during early mouse embryogenesis

Lolas, M, Valenzuela, PD, Tjian, R, Liu, Z

Proc Natl Acad Sci U S A 2014
11358869 FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse

Wrana, JL, Labbé, E, Attisano, L, Hoodless, PA, Rossant, J, Pye, M, Chazaud, C

Genes Dev 2001
11358868 The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse

Ikawa, Y, Mochida, K, Meno, C, Shiratori, H, Sakai, Y, Yamamoto, M, Saijoh, Y, Hamada, H

Genes Dev 2001
19103193 Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis

Tokunaga, T, Motoyama, J, Yamada, G, Aoto, K, Shikata, Y, Shioda, S, Imai, H, Matsumaru, D

Dev Biol 2009
26845388 Notochord morphogenesis in mice: Current understanding & open questions

Nowotschin, S, Hadjantonakis, AK, Balmer, S

Dev Dyn 2016
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