Opposing Nodal and BMP Signals Regulate Left–Right Asymmetry in the Sea Urchin Larva

Abstract

A left-right patterning study in developing sea urchin shows that the opposing roles of Nodal and BMP signaling in patterning the left-right axis are conserved in deuterostomes.

Abstract

Nodal and BMP signals are important for establishing left-right (LR) asymmetry in vertebrates. In sea urchins, Nodal signaling prevents the formation of the rudiment on the right side. However, the opposing pathway to Nodal signaling during LR axis establishment is not clear. Here, we revealed that BMP signaling is activated in the left coelomic pouch, specifically in the veg2 lineage, but not in the small micromeres. By perturbing BMP activities, we demonstrated that BMP signaling is required for activating the expression of the left-sided genes and the formation of the left-sided structures. On the other hand, Nodal signals on the right side inhibit BMP signaling and control LR asymmetric separation and apoptosis of the small micromeres. Our findings show that BMP signaling is the positive signal for left-sided development in sea urchins, suggesting that the opposing roles of Nodal and BMP signals in establishing LR asymmetry are conserved in deuterostomes.

Author Summary

Bilateral animals that are externally symmetric in appearance often have internal organs that are asymmetric with respect to the left and right sides of their bodies. Two signals, Nodal and BMP, have been shown to establish this asymmetry during vertebrate embryogenesis. We investigate here whether the same mechanisms that establish left-right patterning in vertebrates are conserved in invertebrate animals, specifically in the California purple sea urchin. This sea urchin passes through various stages in its lifecycle before developing to adulthood, including a feeding larva stage in which the tissue that goes on to form the adult, the so-called adult rudiment, forms on the left side. Previous studies have shown that right-sided Nodal signaling in sea urchins prevents the formation of the adult rudiment. In this study, we show that BMP signaling is activated on the left side and is required for the development of this left-sided structure. We also demonstrate that Nodal signaling blocks BMP activity and induces apoptosis of the tissue that forms the adult rudiment on the right side. We propose that the roles of Nodal and BMP signals in establishing left-right asymmetry are evolutionarily conserved.