Dorsoventral patterning by the Chordin-BMP pathway: a unified model from a pattern-formation perspective for drosophila, vertebrates, sea urchins and nematostella

Abstract

Conserved from Cnidarians to vertebrates, the dorsoventral (DV) axis is patterned by the Chordin-BMP pathway. However, the functions of the pathway's components are very different in different phyla. By modeling it is shown that many observations can be integrated by the assumption that BMP, acting as an inhibitory component in more ancestral systems, became a necessary and activating component for the generation of a secondary and antipodal-located signaling center. The different realizations seen in vertebrates, Drosophila, sea urchins and Nematostella allow reconstruction of a chain of modifications during evolution. BMP-signaling is proposed to be based on a pattern-forming reaction of the activator-depleted substrate type in which BMP-signaling acts via pSmad as the local self-enhancing component and the depletion of the highly mobile BMP-Chordin complex as the long-ranging antagonistic component. Due to the rapid removal of the BMP/Chordin complex during BMP-signaling, an oriented transport and "shuttling" results, although only ordinary diffusion is involved. The system can be self-organizing, allowing organizer formation even from near homogeneous initial situations. Organizers may regenerate after removal. Although connected with some losses of self-regulation, for large embryos as in amphibians, the employment of maternal determinants is an efficient strategy to make sure that only a single organizer of each type is generated. The generation of dorsoventral positional information along a long-extended anteroposterior (AP) axis cannot be achieved directly by a single patch-like organizer. Nature found different solutions for this task. Corresponding models provide a rationale for the well-known reversal in the dorsoventral patterning between vertebrates and insects.

On the evolution of bilaterality

“…Even if all medusozoans prove to lack some of the crucial components of the BMP ligand shuttling machinery, this can only serve as circumstantial evidence against the independent emergence of the two orthogonal body axes regulated by Wnt/β-catenin and BMP signalling in anthozoan Cnidaria and Bilateria. Moreover, BMP signalling networks differ significantly between cnidarians and bilaterians (Genikhovich et al, 2015), and recent mathematical modelling has shown that the formation of two orthogonal body axes from an initial state when Wnt and BMP signalling networks act along the same axis can occur easily (Meinhardt, 2015); it requires the BMP signalling network to contain a negative-feedback loop regulating chordin expression, and to be under control of the Wnt signalling network (Meinhardt, 2015). If this was the case, the formation of the ur-bilaterian, as well as of the ur-anthozoan, was accompanied by the uncoupling of the initially collinear Wnt and BMP signalling gradients.…”

What determines direction of asymmetry: genes, environment or chance?

“…Across vertebrates, the two body axes (AP and DV) are patterned by a combination of Nodal and BMP signalling [22,23]. More broadly, although the functions of some components vary, the Chordin -BMP pathway appears to pattern the DV axis in most animals [24]. Improbable as it might seem, the midplane defined by these axes can be remarkably crisp (figure 6a), so it is more than just a hypothetical construct.…”

Models for patterning primary embryonic body axes: The role of space and time

“…Maternal determinants are not required if the embryo starts as a small nest of cells such as in mouse or chick development. In this case, the self-regulatory features of pattern-forming reactions allow complete development in fragments even if the organizer is removed [6]. The formation of several embryos after early fragmentation of a chicken embryo is an example [7].…”