Ascagni, M. | bioRxiv Science

bioRxiv2024

A feather star is born: embryonic development and nervous system organization in the crinoid Antedon mediterranea

BackgroundCrinoids belong to the phylum Echinodermata, marine invertebrates with a highly derived pentaradial body plan. As the only living members of the Pelmatozoa, the sister group to other extant echinoderms, crinoids are in a key phylogenetic position to reconstruct the evolutionary history of this phylum. However, the development of crinoids has been scarcely investigated, limiting their potential for comparative studies. Many crinoids are difficult to collect in the wild and embryo manipulation is challenging. Conversely, the Mediterranean feather star Antedon mediterranea can be found in shallow waters and has been used for experimental studies, most notably to investigate regeneration. ResultsThe aim here was to establish A. mediterranea as an experimental system for developmental biology. To accomplish this, we set up a method for culturing embryos in vitro from zygote to hatching larva stage that allowed us to define a developmental timeline and a standardized staging system for this species. We then optimized protocols to characterize the development of the main structures of the feather star body plan, using a combination of microscopy techniques and whole mount immunohistochemistry and in situ hybridization chain reaction. Focusing on the nervous system, we show that the larval apical organ includes a combination of serotonergic, GABAergic and glutamatergic neurons that form under the influence of a conserved anterior molecular signature. The larval neural plexus is instead composed of glutamatergic neurons and develops during the formation of the ciliary bands. Larval neurons disappear at metamorphosis, and the ectoneural and entoneural components of the adult nervous system develop early in post-metamorphic stages. Furthermore, the oral ectoderm that contains the ectoneural system acquires an "anterior" signature expressing Six3/6 and Lhx2/9 orthologs. ConclusionsOur results deepen our knowledge on crinoid development and provide new techniques to investigate feather star embryogenesis, promoting the use of A. mediterranea in developmental and evolutionary biology. This in turn will pave the way for the inclusion of crinoids in comparative studies to understand the origin of the echinoderm body plan and clarify many unanswered questions on deuterostome evolution.

developmental biology↗

bioRxiv2022

Linking acetylated alpha-Tubulin redistribution to alpha-Synuclein pathology in brain of Parkinson's disease patients

Highly specialized microtubules in neurons are crucial to the health and disease of the nervous system, and their properties are strictly regulated by different post-translational modifications, including -Tubulin acetylation. An imbalance in the levels of acetylated -Tubulin has been reported in experimental models of Parkinsons disease (PD) whereas pharmacological or genetic modulation that leads to increased acetylated -Tubulin successfully rescues axonal transport defects and inhibits -Synuclein aggregation. However, the role of acetylation of -Tubulin in the human nervous system is largely unknown as most studies are based on in vitro evidence. To capture the complexity of the pathological processes in vivo, we analysed post-mortem human brain of PD patients and control subjects. In the brain of PD patients at Braak stage 6, we found a redistribution of acetylated -Tubulin, which accumulates in the neuronal cell bodies in subcortical structures but not in the cerebral cortex, and decreases in the axonal compartment, both in the central and peripheral nervous system. High-resolution and 3D reconstruction analysis linked acetylated -Tubulin redistribution to -Synuclein oligomerization, leading us to propose a model for Lewy body (LB) morphogenesis. Finally, for the first time in post-mortem human brain, we observed threadlike structures, resembling tunnelling nanotubes that contain -Synuclein oligomers and are associated with acetylated -Tubulin enriched neurons. In conclusion, we disclose a novel aspect of LB morphogenesis, indicating the role of acetylated -Tubulin in PD, that may provide clues to design novel therapeutic interventions.

neuroscience↗