| Autor: |
Anselmi C; Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Kowarsky M; Department of Physics, Stanford University, Stanford, CA 94305., Gasparini F; Dipartimento di Biologia, Università degli Studi di Padova, 35131, Padova, Italy., Caicci F; Dipartimento di Biologia, Università degli Studi di Padova, 35131, Padova, Italy., Ishizuka KJ; Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950., Palmeri KJ; Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950., Raveh T; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Sinha R; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Neff N; Chan Zuckerberg Biohub, San Francisco CA 94158., Quake SR; Chan Zuckerberg Biohub, San Francisco CA 94158.; Departments of Applied Physics and Bioengineering, Stanford University, Stanford, CA 94305., Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.; Chan Zuckerberg Biohub, San Francisco CA 94158.; Department of Biology, Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950., Voskoboynik A; Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.; Chan Zuckerberg Biohub, San Francisco CA 94158.; Department of Biology, Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950., Manni L; Dipartimento di Biologia, Università degli Studi di Padova, 35131, Padova, Italy. |
| Abstrakt: |
Colonial tunicates are marine organisms that possess multiple brains simultaneously during their colonial phase. While the cyclical processes of neurogenesis and neurodegeneration characterizing their life cycle have been documented previously, the cellular and molecular changes associated with such processes and their relationship with variation in brain morphology and individual (zooid) behavior throughout adult life remains unknown. Here, we introduce Botryllus schlosseri as an invertebrate model for neurogenesis, neural degeneration, and evolutionary neuroscience. Our analysis reveals that during the weekly colony budding (i.e., asexual reproduction), prior to programmed cell death and removal by phagocytes, decreases in the number of neurons in the adult brain are associated with reduced behavioral response and significant change in the expression of 73 mammalian homologous genes associated with neurodegenerative disease. Similarly, when comparing young colonies (1 to 2 y of age) to those reared in a laboratory for ∼20 y, we found that older colonies contained significantly fewer neurons and exhibited reduced behavioral response alongside changes in the expression of 148 such genes (35 of which were differentially expressed across both timescales). The existence of two distinct yet apparently related neurodegenerative pathways represents a novel platform to study the gene products governing the relationship between aging, neural regeneration and degeneration, and loss of nervous system function. Indeed, as a member of an evolutionary clade considered to be a sister group of vertebrates, this organism may be a fundamental resource in understanding how evolution has shaped these processes across phylogeny and obtaining mechanistic insight. |
