Ceccatelli, S. | Search bioRxiv

bioRxiv2023

Oligodendrocyte precursor cells engulf synapses in a model of the developing human forebrain

Recent work in animal models suggests the role of oligodendrocyte precursor cells (OPCs) is not limited to oligodendrogenesis. Here, we report that OPCs derived from human induced pluripotent stem cells are capable of engulfing synaptosomes. We then develop a novel multi-lineage forebrain organoid in which OPCs alongside microglia display a spontaneous internalization of synaptic material in their phagolysosomes. Collectively, these findings suggest that OPCs contribute to synapse elimination in the developing human forebrain and provide a versatile platform for evaluating the interplay between microglia and OPCs in remodeling neuronal circuits in health and disease.

neuroscience↗

bioRxiv2022

Early pre-neural serotonin modulates balance of late monoamines and behavioral patterns in fish model system

The presence of serotonergic system during early pre-neural development is enigmatic and conserved amongst all studied invertebrate and vertebrate animals. We took advantage of zebrafish model system to address what is the role of early serotonin before first neurons form. Unexpectedly, we experimentally revealed the existence of delayed developmental neurogenic and behavioral effects resulting from the manipulations of pre-neural (zygote, blastula and gastrula) serotonergic system. In particular, the delayed effects included differences in the synthesis of serotonin in early serotonergic neurons in the central nervous system as well as in behavioral alterations after habituation in zebrafish larvae. These effects appeared as highly specific and did not coincide with any major abnormalities. The same manipulations of the serotonergic system at neural developmental stages did not show such effects, which confirms that early effects of serotonergic system manipulation are not based on retained serotonin in embryonic cells. Accordingly, gene expression analysis demonstrated specific changes only in response to the elevation of early pre-neural serotonin, which included the delayed and pre-mature onsets of different gene expression programs. Taken together, our results introduce a novel function of early pre-neural serotonergic system in a vertebrate embryo - tuning and fine control of specific mechanisms at later neural developmental stages that result in a mild variation of a behavioral adaptive spectrum.

developmental biology↗