Multiple Forms of Neural Cell Death in the Cyclical Brain Degeneration of A Colonial Chordate

Chiara Anselmi, Federico Caicci, Tommaso Bocci, Matteo Guidetti, Alberto Priori, Veronica Giusti, Tom Levy, Tal Raveh, Ayelet Voskoboynik, Irving L. Weissman, Lucia Manni

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Human neuronal loss occurs through different cellular mechanisms, mainly studied in vitro. Here, we characterized neuronal death in B. schlosseri, a marine colonial tunicate that shares substantial genomic homology with mammals and has a life history in which controlled neurodegeneration happens simultaneously in the brains of adult zooids during a cyclical phase named takeover. Using an ultrastructural and transcriptomic approach, we described neuronal death forms in adult zooids before and during the takeover phase while comparing adult zooids in takeover with their buds where brains are refining their structure. At takeover, we found in neurons clear morphologic signs of apoptosis (i.e., chromatin condensation, lobed nuclei), necrosis (swollen cytoplasm) and autophagy (autophagosomes, autolysosomes and degradative multilamellar bodies). These results were confirmed by transcriptomic analyses that highlighted the specific genes involved in these cell death pathways. Moreover, the presence of tubulovesicular structures in the brain medulla alongside the over-expression of prion disease genes in late cycle suggested a cell-to-cell, prion-like propagation recalling the conformational disorders typical of some human neurodegenerative diseases. We suggest that improved understanding of how neuronal alterations are regulated in the repeated degeneration–regeneration program of B. schlosseri may yield mechanistic insights relevant to the study of human neurodegenerative diseases.

Original languageEnglish
Article number1041
Issue number7
StatePublished - 1 Apr 2023
Externally publishedYes


  • apoptosis
  • autophagy
  • colonial chordate
  • lysosomal cell death
  • necroptosis

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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