ERK1/2 is an ancestral organising signal in spiral cleavage

Abstract

SUMMARYEmbryonic organisers are signalling centres that instruct the establishment of body plans during animal embryogenesis, thus underpinning animal morphological diversity. In spiral cleavage – a stereotypic developmental programme ancestral to 14, nearly half, of the major animal groups (e.g., molluscs, annelids and flatworms), a cell known as the D-quadrant organiser defines cell fates and the body axes. ERK1/2 specifies the embryonic organiser in molluscs, yet how this signalling cascade exerts organising activity and whether this role is conserved in other spiral cleaving groups is unclear. Here, we demonstrate that ERK1/2 promotes the specification and inductive activity of the D-quadrant organiser in Owenia fusiformis, an early-branching annelid exhibiting ancestral developmental traits. In this species, active di-phosphorylated ERK1/2 mediated by FGF receptor activity localises to the 4d micromere, establishing the bilateral symmetry and specifying the hindgut and trunk mesodermal progenitor. Accordingly, impairing FGFR and ERK1/2 activity, as well as cell communication results in embryos developing anteroventrally radialised. Differential transcriptomic profiling shows the ParaHox cdx and the Notch ligand delta as FGFR/ERK1/2 downstream targets in 4d, further revealing that 4d specification instructs the expression of mesodermal and posterodorsal genes in neighbouring cells, putatively via the Notch pathway. The instructing role of ERK1/2 in the D-quadrant organiser is thus shared between O. fusiformis and molluscs, representing an ancestral trait of spiral cleavage. Altogether, our study begins to dissect the gene network promoting axial patterning and posterior growth in spiral cleavage, revealing extensive mechanistic diversification in body plan specification despite overall conservation of cleavage patterns in Spiralia.