Bevilacqua, A. | bioRxiv Science

bioRxiv2024

Trigeminal ganglion and tooth innervation modifications following genetic and pharmacological Nogo-A inhibition

Nogo-A is a major regulator of neural development and regeneration, but its role in tooth innervation remains largely unknown. Neurons from trigeminal ganglia support teeth homeostasis and regeneration, and disorders of their function could have significant pathophysiological consequences. In this study, we show that Nogo-A is expressed in the trigeminal ganglia and in the neurons innervating the teeth, and that its deletion affects both the number and patterning of neurons in teeth. In organotypic cultures, Nogo-A blocking antibodies affect the trigeminal ganglia-derived neuronal outgrowths and allow premature innervation of tooth germs. RNA sequencing analysis revealed that Nogo-A deletion induces alterations linked to functions at synapses and interference with neurotrophin signalling during the differentiation and maturation of trigeminal neurons. Taken together, these results reveal for the first time the importance of Nogo-A as a major regulator of tooth innervation and point to its potential as a clinical therapeutic target.

neuroscience↗

bioRxiv2023

Chemotactic interactions drive migration ofmembraneless active droplets

In nature, chemotactic interactions are ubiquitous and play a critical role in driving the collective behaviour of living organisms. Reproducing these interactions in vitrois still a paramount challenge due to the complexity of mimicking and controlling cellular features, such as metabolic density, cytosolic macromolecular crowding and cellular migration, on a microorganism size scale. Here we generate enzymatically-active cell-size droplets able to move freely and, by following a chemical gradient, able to interact with the surrounding droplets in a collective manner. The enzyme within the droplets generates a pH gradient that extends outside the edge of the droplets. We discovered that the external pH gradient triggers droplet migration and controls its directionality, which is selectively towards the neighbouring droplets. Hence, by changing the enzyme activity inside the droplet we tuned the droplet migration speed. Further, we showed that these cellular-like features can facilitate the reconstitution of a simple and linear protometabolic pathway with improved overall activity. Our work suggests that simple and stable membraneless droplets can be applied to reproduce complex biological phenomena opening new perspectives as bioinspired materials and synthetic biology tools.

biochemistry↗