The anti-neural role of BMP signaling is a consequence of its ancestral function in dorsoventral patterning.

Overview

1. Department of Neurosciences and Developmental Biology, University of Vienna, Vienna, Austria
2. Vienna Doctoral School of Ecology and Evolution (VDSEE), University of Vienna, Vienna, Austria
3. Konrad Lorenz Institute for Evolution and Cognition Research, Klosterneuburg, Austria
4. Department of Evolutionary Biology, University of Vienna, Vienna, Austria
5. Haus des Meeres, Vienna, Austria
6. Tiergarten Schönbrunn, Vienna, Austria

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). Furthermore, we analyze BMP signaling activity in the cubozoan jellyfish Tripedalia and the scyphozoan jellyfish Stomolophus and prove that BMP signaling in parts of the diffuse 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 nonmodel 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 may have been in promoting neurogenesis. We propose that the “anti-neural” function of BMP signaling in vertebrates and arthropods is a consequence of its global role in the dorsoventral patterning of the ectoderm.

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Data

Datasets cited

• bioproject:PRJNA1269470, at NCBI BioProject; found in “Data Availability”

Other data links

• ncbi.nlm.nih.gov/bioproject/1441074, NCBI; found in “Data Availability”

Data Availability

Newly generated sequencing data is deposited as bioprojects at https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1269470 and http://www.ncbi.nlm.nih.gov/bioproject/1441074. All code required to reproduce the computational analyses of this study can be found on https://github.com/Genikhovich-Lab/ and, additionally, at 10.5281/zenodo.19686897 (https://doi.org/10.5281/zenodo.19686897) and 10.5281/zenodo.19686882 (https://doi.org/10.5281/zenodo.19686882). All other relevant data are within the paper and its Supporting information files.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

• Funding: added Österreichischen Akademie der Wissenschaften; Austrian Science Fund: P 34665, P32705, PAT2395824; Universität Wien; Universitetet i Bergen; Lomonosov Moscow State University

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Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 10 MeSH terms, 105 references.

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This paper

Knabl, P., Ordoñez, J. F., Montenegro Cabrera, J. D., Abed-Navandi, D., Halbauer, R., Link, O., Wollesen, T., & Genikhovich, G. (2026). The anti-neural role of BMP signaling is a consequence of its ancestral function in dorsoventral patterning. PLoS biology, 24(5), e3003803. https://doi.org/10.1371/journal.pbio.3003803

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