Formation of lateral plate mesoderm

Formation of lateral plate mesoderm Subsets of mesoderm that have different developmental fates are produced along the primitive streak from posterior to anterior (reviewed in Arnold and Robertson 2009, Ferretti and Hadjantonakis 2019, Prummel et al. 2020, Zhai et al. 2021). In mice these subsets are (from posterior to anterior): extraembryonic mesoderm; lateral mesoderm that will form heart, limbs, and blood; presomitic mesoderm that will form somites; axial mesoderm that will form the notochord; and, finally, definitive endoderm. In humans and other primates, extraembryonic mesoderm appears to form from the hypoblast prior to gastrulation so lateral plate mesoderm is the first type of mesoderm to form at the primitive streak.
In the lateral plate mesoderm, a self-reinforcing transcription loop is initiated by Hedgehog signaling from the adjacent primitive endoderm (inferred from mouse homologs in Astorga and Carlsson 2007, Becker et al. 1997). Hedgehog proteins SHH and IHH activate expression of FOXF1, a marker of the lateral plate mesoderm following its induction (inferred from mouse homologs in Rojas et al. 2005, Astorga and Carlsson 2007). BMP4 may also activate FOXH1 in the primitive streak and lateral plate mesoderm (inferred from Xenopus homologs in Tseng et al. 2004). FOXF1 activates expression of BMP4 and BMP4 together with FOXF1 activate GATA4 (inferred from mouse homologs in Rojas et al. 2005).. BMP4 maintains the expression of FOXF1. GATA4 maintains its own expression and the expression of BMP4. FOXF1 and GATA4 then activate expression of downstream genes that further differentiate the lateral plate mesoderm. In zebrafish, the combined activity of Eomesodermin, FoxH1, and Mixl1, together with Smad proteins induces lateral plate mesoderm and this mechanism may be shared across chordates (Prummel et al. 2019).