Observing the birth of the nervous system

Researchers from Kiel University show how the nerve network in the freshwater polyp Hydra self-organises during embryonic development under the influence of environmental factors including the microbiome

A fundamental question in neurobiology and developmental biology is how multicellular organisms form differently organised nervous systems during their individual development, which enable them to develop a species-specific behavioural repertoire. However, the high neuronal complexity of many organisms makes it difficult to analyse the mechanisms involved. A research team led by Thomas Bosch, Professor of Cell and Developmental Biology at Kiel University, has now used the example of the freshwater polyp Hydra, an established model organism for neurobiology and microbiome research, to gain new insights into the factors that determine the formation of the nervous system during the embryonic development of animals.

Thanks to an interdisciplinary research approach consisting of innovative imaging methods for Ca²⁺ activity of nerve cells and bioinformatic analyses, the Kiel team, which is involved in the Collaborative Research Centre (CRC) 1182 “Origin and Function of Metaorganisms” and CRC 1461 “Neurotronics” was able to trace the development from the activation of individual neurons to a functioning nerve network in detail. Previous theories assumed that phylogenetically old neuronal circuits are a network of randomly connected nerve cells. In collaboration with colleagues from Ruhr University Bochum, among others, the Kiel scientists have now been able to show that the nerve network organises itself autonomously through the activity of individual neurons and the resulting interconnections. Thus, the adult animals ultimately acquire their broad spectrum of behaviour, which includes contraction patterns, various types of locomotion as well as feeding.

In addition, the Kiel researchers discovered that, contrary to previous assumptions, this development is not purely genetically determined, but is in fact plastic and can be influenced by environmental factors such as temperature or the presence or absence of natural microbial colonisation of the polyps. Thanks to this plasticity, it seems possible that multicellular organisms can quickly adapt to changing environmental conditions mediated by their nervous system. The research team therefore proposes that the principle of self-organisation and plasticity could apply universally to the neuronal development of multicellular organisms. The new results from the CRC 1182 were published recently in the renowned scientific journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Nerve cells organise themselves via their incipient activity
To observe the to date little researched initial processes involved in the development of the nervous system in an individual organism, the scientists from Kiel studied polyps at a late stage of embryogenesis. The adult animals feature a so-called diffuse nervous system with around 3000 to 5000 individual nerve cells, which are divided into a total of seven nerve populations controlling their behaviour. The research team selected a single group, the N4 population, which was known from previous research to be centrally involved in the feeding behaviour and investigated the development of the neurons involved.

“We observed the embryos over a period of seven and a half hours and took six 30-minute recordings during this time using calcium imaging, which allowed us to track the activity of all individual neurons,” explains Christopher Noack, a scientist in the Cell and Developmental Biology working group at the Zoological Institute. “This showed that initially only individual neurons begin to fire. Over time, small clusters of a few cells form, which interconnect and start to send out a synchronised impulse,” continues CRC 1461 member Noack.

In this way, a dominant community of nerve cells gradually develops, which integrates additional clusters of nerve cells through its increasing activity and thus continues to grow in size. Overall, the animals’ complete nerve network is formed from the prospective mouth area of the embryos down to the rest of the body. “Until recently, it was assumed that the nerve cells first position themselves in the body before activation. However, they begin to differentiate and become active in specific regions of the body, such as the mouth area, in a decentralised way. The process of networking and synchronisation apparently takes place autonomously and self-organised,” continues Noack.

Environmental influences shape the development of the nervous system
To find out whether the development of the nerve network in Hydra is a purely genetically determined process or depends on additional environmental factors, the Kiel researchers then investigated the influence of the microbiome and temperature. Firstly, they looked at possible effects of temperature changes. “We found that low temperatures create favourable conditions for the formation of the nerve network, also overall speeding up the process,” explains Noack. Warm temperatures, on the other hand, displayed a rather negative effect. “An increase in temperature from 18 to 23 degrees Celsius led to the formation of only smaller groups of neurons. In addition, the typical dominant community could not be established. Instead, many small and weakly connected neuron clusters formed,” explains Noack. These limitations impaired the function of the nerve network, frequently resulting in the disruption of the feeding behaviour: around 40 percent of these animals were no longer able to take up food at elevated temperatures.

In a next step, the researchers investigated whether also the microbiome might affect neuronal development by removing the colonising bacteria from Hydra embryos and then comparing such germ-free specimens with controls still colonised by microbes. “Unlike the wild type, germ-free Hydra embryos show a significantly reduced number of neurons overall. This observation therefore points to the involvement of the microbiome in the development of the nervous system,” emphasises Noack.

Interestingly, embryos that develop in the absence of microbes not only show a lower number of nerve cells overall, but also significantly less connections with other neurons. If such germ-free embryos are subsequently colonised with microbes, this defect is levelled out and the still comparatively few neurons now form a relatively large number of connections. “We suspect that the restoration of the microbiome partially compensates for the impairment of the nervous system through better networking of the existing cells, which despite their lower number can still maintain their functions,” says Bosch, who heads the Kiel Life Science (KLS) research area at Kiel University.

According to the researchers, these observations could also be confirmed using other germ-free model organisms, such as fruit flies, zebrafish and mice. How temperature and the microbiome influence the number and connection of nerve cells in detail remains unclear. But the realisation that phylogenetically old neuronal circuits do not begin as randomly connected networks, but form and grow through self-organisation in a dynamic process in which stability and precision are achieved through mechanisms that involve a considerable degree of structural and functional plasticity, is not only of interest in evolutionary and neurobiological terms, but is also relevant for the understanding and design of new types of artificial neuronal networks.

“Overall, our new results highlight that the development of the nervous system can be influenced by environmental conditions in general and that the processes involved show a high degree of adaptability or plasticity, with the microbiome in particular possibly playing a crucial role. Once again, these findings underline the fundamental importance of the natural microbial colonisation for the development and function of multicellular organisms,” summarises Bosch.

Original publication:
Christopher Noack, Sebastian Jenderny, Christoph Giez, Ornina Merza, Lisa-Marie Hofacker, Jörg Wittlieb, Urska Repnik, Marc Bramkamp, Karlheinz Ochs, Thomas C. G. Bosch (2025): Assembly of a functional neuronal circuit in embryos of an ancestral metazoan is influenced by temperature and the microbiome. PNAS First published: 05. June 2025 doi.org/10.1073/pnas.250122512

Images are available for download:
www.uni-kiel.de/de/pressemitteilungen/2025/097-noack-pnas-authors.JPG
Caption: The research team, pictured here are Prof. Thomas Bosch, Christopher Noack and Jörg Wittlieb (from right to left), discovered that the Hydra‘s nerve network is organised in an activity-dependent manner during embryonic development and is influenced by environmental factors such as temperature and microbiome.
© Christian Urban, Kiel University

www.uni-kiel.de/de/pressemitteilungen/2025/097-noack-pnas-neurons.jpg
Caption: At different stages of development, specific nerve cell populations and their connections can only be found in the future head and foot region of Hydra (neurons coloured green, additionally on the left in red: actin filaments that form the cytoskeleton of the cells).
© Christopher Noack

www.uni-kiel.de/de/pressemitteilungen/2025/097-noack-pnas-screen.JPG
Caption: The researchers assume that even early nervous systems have the ability to adapt to rapidly changing environmental conditions and that the principle of self-organisation and plasticity could apply universally to the neuronal development of multicellular organisms.
© Christian Urban, Kiel University

Contact:
Prof. Thomas Bosch
Cell and Developmental Biology
Zoological Institute, Kiel University
Phone +49 431-880-4170
Email: tbosch@zoologie.uni-kiel.de

More information:
Cell and Developmental Biology
Zoological Institute, Kiel University:
www.bosch.zoologie.uni-kiel.de

Priority research area Kiel Life Science (KLS),
Kiel University:
www.kls.uni-kiel.de