The anti-neural role of BMP signaling is a side effect of its global function in dorsoventral patterning

Abstract

In Bilateria with centralized nervous systems (e.g. in vertebrates or arthropods), the minimum of the BMP signaling activity gradient defines the position of the central nervous system. BMP-dependent patterning of the secondary body axis is ancestral for Bilateria and possibly also for the bilaterian sister clade Cnidaria. However, the variety of levels of centralization of the nervous systems in Bilateria - from diffuse to fully centralized - as well as the lack of centralization of the nervous system in Cnidaria, suggest that BMP signaling cannot be perceived as a universally "anti-neural" signal. Here we use transgenic reporter lines in the anthozoan cnidarian Nematostella to show that BMP signaling is active in distinct neuronal populations. Moreover, attenuation of BMP signaling followed by RNA-Seq shows that BMP signaling is a positive regulator of many neuronal genes, including the top-tier neural progenitor marker soxB(2). Further, we analyze BMP signaling activity in the true jellyfish Aurelia and box jellyfish Tripedalia proving that BMP signaling in the diffuse cnidarian nervous system is not an anthozoan but an ancestral cnidarian feature, shared by anthozoans and medusozoans. Finally, we show that the highly centralized ventral nervous system of the non-model spiralian, the chaetognath Spadella, forms out of paired BMP signaling-positive domains on the lateral sides of the embryo. Together, our data suggest that one of the ancestral roles of BMP signaling was in promoting neurogenesis. We propose that the "anti-neural" function of BMP signaling in vertebrates and arthropods is a side effect of its global role in the dorsoventral patterning of the ectoderm.