Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect

摘要

How an animal develops from a fertilized egg has fascinated scientists for decades. As such, much effort has gone into answering the related question what makes the belly (or underside) of an animal develop differently from its back? Like almost all other biological processes, the development of an embryo is controlled by interactions between different molecules within cells and tissues. Some of these molecules promote the activity of others; some have the opposite effect; and together these molecules and their interactions form ‘signaling networks’. One such network, which involves a protein called BMP, is needed to establish the belly-to-back axis of nearly all animals. However, insects are a unique exception. Most insects (including flies, beetles and wasps) use a different signaling network to control their development from their belly to their back, one that involves a protein called Toll instead. This is unexpected because, in other animals, Toll proteins are best known for their role in the immune system; and it remains unclear how Toll signaling came to be involved in insect development. Now, Sachs, Chen et al. have studied an insect—called the milkweed bug—that is unlike most insects in that it does not have a larval stage (i.e., a maggot or a caterpillar) in its life-cycle. This characteristic makes the milkweed bug more similar to the ancestor of all insects, and thus makes it an excellent model to study how the Toll protein took over from BMP in insect development. First, Sachs, Chen et al. experimentally reduced BMP signaling in milkweed bug embryos. This caused the embryos to develop features all around their bodies that are normally only associated with the animal's underside. In other insects, the development of these so-called ‘ventral’ features is typically controlled by Toll signaling; but in the milkweed bug this activity instead depends on a protein called Sog. Indeed, when Sachs, Chen et al. experimentally reduced both BMP and Toll signaling, the effect was the same as having reduced only BMP signaling, implying that Toll is not needed. Instead, Toll increased the level of the Sog protein up to a particular threshold. Above this threshold, Sog and BMP control each other to set out the animal's body plan. As insects evolved, it seems likely that Toll transitioned from being a trigger of BMP signaling to an important controller of insect development in its own right. But why was Toll put in the egg in the first place? It is possible that Toll was required to protect the eggs of early insects from attack by bacteria and fungi. Future work will now test this assumption and aim to explain how and why the Toll protein changed its role—from immunity to development—during evolution.