The nervous systems of cnidarians, pre-bilaterian animals that diverged close to the base of the metazoan radiation, are structurally simple and thus have great potential to inform us about basic structural and functional principles of neural circuits. Unfortunately, cnidarians have thus far been relatively intractable to electrophysiological and genetic techniques and consequently have been largely passed over by neurobiologists. However, recent advances in molecular and imaging methods are fueling a renaissance of interest in and research into cnidarians nervous systems. Here, we review current knowledge on the nervous systems of some cnidarian species and propose that researchers should seize this opportunity and undertake the study of this phylum as strategic experimental systems with great basic and translational relevance for neuroscience.

Spontaneous contractile activity, such as gut peristalsis, is ubiquitous in animals and is driven by pacemaker cells. In humans, disruption of the contraction pattern leads to gastrointestinal conditions, which are also associated with gut microbiota dysbiosis. Spontaneous contractile activity is also present in animals lacking gastrointestinal tract. Here we show that spontaneous body contractions in Hydra are modulated by symbiotic bacteria. Germ-free animals display strongly reduced and less regular contraction frequencies. These effects are partially restored by reconstituting the natural microbiota. Moreover, soluble molecule(s) produced by symbiotic bacteria may be involved in contraction frequency modulation. As the absence of bacteria does not impair the contractile ability itself, a microbial effect on the pacemakers seems plausible. Our findings indicate that the influence of bacteria on spontaneous contractile activity is present in the early-branching cnidarian hydra as well as in Bilateria, and thus suggest an evolutionary ancient origin of interaction between bacteria and metazoans, opening a window into investigating the roots of human motility disorders.

Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability to generate rhythmic bursts of action potential. Recent work has identified rhythmic gut contractions in human, mice, and hydra to be dependent on both neurons and the resident microbiota. However, little is known about the evolutionary origin of these neurons and their interaction with microbes. In this study, we identified and functionally characterized prototypical ANO/SCN/TRPM ion channel-expressing pacemaker cells in the basal metazoan Hydra by using a combination of single-cell transcriptomics, immunochemistry, and functional experiments. Unexpectedly, these prototypical pacemaker neurons express a rich set of immune-related genes mediating their interaction with the microbial environment. Furthermore, functional experiments gave a strong support to a model of the evolutionary emergence of pacemaker cells as neurons using components of innate immunity to interact with the microbial environment and ion channels to generate rhythmic contractions.

Summary1. In seasonal environments, modifications in the phenology of life-history events can alter the strength of time constraints experienced by organisms. Offspring can compensate for a change in timing of hatching by modifying their growth and development trajectories. However, intra-and interspecific interactions may affect these compensatory responses, in particular if differences in phenology between cohorts lead to significant priority effects (i.e. the competitive advantage that early-hatching individuals have over late-hatching ones). 2. Here, we conducted a factorial experiment to determine whether intraspecific priority effects can alter compensatory phenotypic responses to hatching delay in a synchronic breeder by rearing moor frog (Rana arvalis) tadpoles in different combinations of phenological delay and food abundance. 3. Tadpoles compensated for the hatching delay by speeding up their development, but only when reared in groups of individuals with identical hatching phenology. In mixed phenology groups, strong competitive effects by non-delayed tadpoles prevented the compensatory responses and delayed larvae metamorphosed later than in single phenology treatments. Nondelayed individuals gained advantage from developing with delayed larvae by increasing their developmental and growth rates as compared to single phenology groups. 4. Food shortage prolonged larval period and reduced mass at metamorphosis in all treatments, but it did not prevent compensatory developmental responses in larvae reared in single phenology groups. 5. This study demonstrates that strong intraspecific priority effects can constrain the compensatory growth and developmental responses to phenological change, and that priority effects can be an important factor explaining the maintenance of synchronic life histories (i.e. explosive breeding) in seasonal environments.

Organisms are exposed to multiple sources of stress in nature. When confronted with a stressful period affecting growth and development, compensatory responses allow the restoration of individual fitness, providing an important buffering mechanism against climatic and other environmental variability. However, tradeoffs between increased growth/development and other physiological traits are predicted to prevent these high growth and development rates from becoming constitutive. Here, we investigated how compensatory responses in growth and development affect immune responses. By using low temperature to stop embryonic development, we exposed moor frog Rana arvalis tadpoles to two levels of time‐constraints: non‐delayed hatching and 12‐day delayed hatching. In a common garden experiment, we recorded larval growth and development, as well as their immune response, measured as the inflammatory reaction after the injection of phytohaemagglutinin (PHA). Tadpoles originating from delayed hatching treatments had a lower immune response to PHA challenge than those from the non‐delayed hatching treatment. In general, tadpoles from the delayed hatching treatment reached metamorphosis faster and at a smaller size than control tadpoles. However, immune‐challenged tadpoles were not able to accelerate their development in response to delayed hatching. Our results indicate that 1) the innate immune response can be reduced in organisms undergoing compensatory developmental responses in growth and development and 2) compensatory capacity can be reduced when organisms are immunologically challenged. These dual findings reveal the complexity of handling multiple stressors and highlight the importance of examining the costs and limits of mounting an immune response in the context of increasing phenological instability ascribed to climate change.

The head represents the most complex part of the body and a distinctive feature of the vertebrate body plan. This intricate structure is assembled during embryonic development in the four-dimensional process of morphogenesis. The head integrates components of the central and peripheral nervous system, sensory organs, muscles, joints, glands, and other specialized tissues in the framework of a complexly shaped skull. The anterior part of the head is referred to as the face, and a broad spectrum of facial shapes across vertebrate species enables different feeding strategies, communication styles, and diverse specialized functions. The face formation starts early during embryonic development and is an enormously complex, multi-step process regulated on a genomic, molecular, and cellular level. In this review, we will discuss recent discoveries that revealed new aspects of facial morphogenesis from the time of the neural crest cell emergence till the formation of the chondrocranium, the primary design of the individual facial shape. We will focus on molecular mechanisms of cell fate specification, the role of individual and collective cell migration, the importance of dynamic and continuous cellular interactions, responses of cells and tissues to generated physical forces, and their morphogenetic outcomes. In the end, we will examine the spatiotemporal activity of signaling centers tightly regulating the release of signals inducing the formation of craniofacial skeletal elements. The existence of these centers and their regulation by enhancers represent one of the core morphogenetic mechanisms and might lay the foundations for intra- and inter-species facial variability.

21 (A.K.) 22 23 2 1 Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability to 2 generate rhythmic bursts of action potential. Recent work has identified rhythmic gut 3 contractions in human, mice and hydra to be dependent on both neurons and the resident 4 microbiota. However, little is known about the evolutionary origin of these neurons and 5 their interaction with microbes. In this study, we identified and functionally characterized 6 prototypical ANO/SCN/TRPM ion channel expressing pacemaker cells in the basal 7 metazoan Hydra by using a combination of single-cell transcriptomics, immunochemistry, 8 and functional experiments. Unexpectedly, these prototypical pacemaker neurons express a 9 rich set of immune-related genes mediating their interaction with the microbial 10 environment. Functional experiments validated a model of the evolutionary emergence of 11 pacemaker cells as neurons using components of innate immunity to interact with the 12