Biology subjects

Wittlieb, J.

Publications and source records attributed to Wittlieb, J..

5 recordsLinked to original sources

bioRxiv2026

Optogenetic perturbations reveal temporal integration of Wnt signaling during pattern formation

The Wnt signaling pathway is a conserved regulator of tissue patterning and regeneration, yet how cells interpret dynamic Wnt inputs to generate robust developmental outcomes remains poorly understood. Here, we establish the first optogenetically activatable Hydra line, enabling precise temporal control of canonical Wnt signaling in vivo. Optogenetic stimulation induced dose-dependent patterning phenotypes whose rate of progression scaled with stimulation intensity. Transcriptomic analysis revealed that distinct combinations of signal intensity and duration converged onto shared transcriptional trajectories and could be described by an effective exposure metric that represents the cumulative signaling input. Functionally, Wnt activation rescued head regeneration under conditions that normally prevent organizer formation, and equivalent regenerative outcomes could be achieved through either strong, short-lived stimulation or weaker, prolonged activation. Together, our results indicate that Hydra tissues decode Wnt signaling through temporal integration of cumulative pathway activity, progressively accumulating transcriptional responses until patterning thresholds are reached. These findings establish a quantitative framework for understanding how dynamic morphogen signaling is translated into stable developmental decisions during regeneration.

developmental biology↗

bioRxiv2024

Assembly of a functional neuronal circuit in embryos of an ancestral metazoan is influenced by environmental signals including the microbiome

Understanding how neural populations evolve to give rise to behavior is a major goal in neuroscience. However, the complexity of the nervous system in most invertebrates and vertebrates complicates the deciphering of underlying fundamental processes. Here, we explore the self-assembly of neural circuits in Hydra, an organism with a simple nervous system but no centralized information processing, to improve the understanding of nervous system evolution. The N4 neuronal circuit in embryos develops through activity-driven self-assembly, where neurons in distinct regions increase connectivity and synchronization. Gap junctions and vesicle-mediated communication between neuronal and non-neuronal cells drive rapid assembly, with the embryos prospective oral region exhibiting the highest neuronal density. An artificial electrical circuit-based model demonstrates dynamic increases in synchronization over time, along with predictions for selective dynamic adaptions of connections. Environmental factors, like temperature and an absent microbiome, modify neural architecture, suggesting the existence of a certain plasticity in neural development. We propose that these fundamental features originated in the last common bilaterian ancestor, supporting the hypothesis that the basic architecture of the nervous system is universal.

neuroscience↗

bioRxiv2024

Genetic interference with HvNotch provides new insights into the role of the Notch-signalling pathway for developmental pattern formation in Hydra

The Notch-signalling pathway plays an important role in pattern formation in Hydra. Using pharmacological Notch inhibitors (DAPT and SAHM1), it has been demonstrated that HvNotch is required for head regeneration and tentacle patterning in Hydra. HvNotch is also involved in establishing the parent-bud boundary and instructing buds to develop feet and detach from the parent. To further investigate the functions of HvNotch, we successfully constructed NICD (HvNotch intracellular domain)-overexpressing and HvNotch-knockdown transgenic Hydra strains. NICD-overexpressing transgenic Hydra showed a pronounced inhibition on the expression of predicted HvNotch-target genes, suggesting a dominant negative effect of ectopic NICD. This resulted in a "Y-shaped" phenotype, which arises from the parent-bud boundary defect seen in polyps treated with DAPT. Additionally, "multiple heads", "two-headed" and "ectopic tentacles" phenotypes were observed. The HvNotch-knockdown transgenic Hydra with reduced expression of HvNotch exhibited similar, but not identical phenotypes, with the addition of a "two feet" phenotype. Furthermore, approximately 20% of the HvNotch-knockdown polyps were unable to regenerate a new head after decapitation. We integrated these findings into a mathematical model based on long-range gradients of signalling molecules underlying sharply defined positions of HvNotch-signalling cells at the Hydra tentacle and bud boundaries.

developmental biology↗

bioRxiv2023

Microbes as part of ancestral neuronal circuits: Bacterial produced signals affect neurons controlling eating behavior in Hydra

Although recent studies indicate the impact of microbes on the central nervous systems and behavior, it remains unclear how the relationship between the functionality of the nervous system, behavior and the microbiota arise. We studied the eating behavior of Hydra, a host that has a simple nervous system and a low-complexity microbiota. To identify the neuronal subpopulations involved, we used a subpopulation specific cell ablation system and calcium imaging. The role of the microbiota was uncovered by reducing the diversity of the natural microbiota. Here, we demonstrate that different neuronal subpopulations are functioning together to control the eating behavior. The microbiota participates in control of the eating behavior since germ-free or mono-colonized animals have drastic difficulties in mouth opening. This was restored by adding a full complement of the microbiota. In summary, we provide a mechanistic explanation of how the eating behavior is controlled in Hydra and how microbes can affect the neuronal circuit. Highlights- Multiple neuronal modules and their networks control complex behavior in an animal lacking a central nervous system. - Its associated microbes participate in these neuronal circuits and influence the eating behavior. - Disorganization of the microbiota negatively impacts this eating behavior. - Glutamate participates in an evolutionary ancient interkingdom language.

animal behavior and cognition↗

bioRxiv2018

Hydra Bcl-2 and TMBIMP family proteins display anti-apoptotic functions

BackgroundMechanisms of programmed cell death differ considerably between animals, plants and fungi. In animals they depend on caspases and Bcl-2 family proteins and this kind of cell death is called apoptosis. Most gene families encoding proteins involved in apoptosis are found in multicellular animals already in the eldest phyla but their functional conservation is still being studied. Much older protein families have cytoprotective functions across all kingdoms of life. This includes the TMBIMP-family, the presence and function of which in early metazoans has not been investigated yet.\n\nMethodsWe quantified apoptosis in transgenic Hydra overexpressing HyBcl-2-like 4. Moreover, we investigated putative TMBIMP-family members in Hydra by sequence comparison. By overexpression of TMBIMP-family members in Hydra and human HEK cells we analysed their subcellular localisation and in one case their capacity to protect cells from camptothecin induced apoptosis.\n\nResultsHyBcl-2-like 4, as previously shown in a heterologous system, was localised to mitochondria and able to protect Hydra epithelial cells from apoptosis. The TMBIMP-family in Hydra includes HyBax-Inhibitor-1, HyLifeguard-1a and -1b and HyLifeguard 4 proteins. HyBax-inhibitor-1 protein was found localised to ER-membranes, HyLifeguard-family members were found at the plasma membrane and in Golgi-vesicles. Moreover, HyBax-inhibitor-1 protected human cells from apoptosis.\n\nConclusionThis work provides the first functional study to support an anti-apoptotic function of Bcl-2 like proteins in pre-bilaterians within a physiological context. Furthermore it illustrates that genes that were \"inherited\" from non-animal ancestors, like the TMBIMP-family, were recruited to carry out cell protective anti-apoptotic functions already in early metazoans.

developmental biology↗