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bioRxiv2026

Evolution Shapes Cortical Interneuron Migration

The cerebral cortex comprises excitatory neurons and inhibitory interneurons originating from distinct forebrain regions. During migration, cortical interneurons (cINs) interact dynamically with neighbouring cells and their microenvironment, contributing to cortical architecture. However, how evolutionary changes in cIN migration shape species-specific cortical development remains unclear. Comparative analyses in mouse, ferret, and human models revealed a conserved migratory sequence but distinct behaviours: human cINs migrate slower, display increased leading-process branching, and exhibit more frequent homotypic repulsive interactions than their mouse and ferret counterparts. These features promote dispersed cortical invasion of cINs in humans and ferrets, contrasting with the stream-like migration observed in mice. Mechanistically, elevated expression of the cytosolic carboxypeptidase CCP1 in human cINs reduces microtubule glutamylation and doublecortin recruitment, thereby facilitating leading-process branching. These findings identify a CCP1-dependent mechanism regulating cIN dispersion and suggest that evolutionary changes in cIN migration contribute to divergent patterns of cortical morphogenesis across mammals.

neuroscience↗

bioRxiv2025

A Sulfotransferase from a Gut Microbe Acts on Diverse Phenolic Sulfate Compounds, Including Acetaminophen Sulfate

Sulfonation is one of the two main phase II detoxification pathways in eukaryotes that transforms non-polar compounds into hydrophilic metabolites. Sulfotransferases catalyze these reactions by transferring a sulfo group from a donor to an acceptor molecule. Human cytosolic sulfotransferases use only 3-phosphoadenosine 5-phosphosulfate (PAPS) as a donor to sulfonate a variety of chemicals. Less understood are microbial aryl-sulfate sulfotransferases (ASSTs), which catalyze sulfo transfer reactions, without utilizing PAPS as a donor. Currently, the identity of physiological sulfo donor substrates remains unknown and sulfo acceptor substrates are underexplored. With this study, we aim to understand the potential contribution of a gut microbial enzyme to sulfonation chemistry by uncovering substrate preferences. Here, we show that a sulfotransferase (BvASST) from the prevalent gut microbe Bacteroides vulgatus (now Phocaeicola vulgatus) is a versatile catalyst that utilizes a wide range of phenolic molecules as substrates that are commonly encountered by the host. With this action, it has the ability to modulate concentrations of donor phenolic sulfates like acetaminophen sulfate, dopamine sulfate, p-coumaric acid sulfate, indoxyl sulfate, and p-cresol sulfate in vitro. Moreover, we report a large adaptability in the acceptor preferences with the evidence of sulfonation for many biologically relevant phenolic molecules including p-coumaric acid, p-cresol, dopamine, acetaminophen, tyramine, and 4-ethylphenol. These results suggest that such gut microbial enzymes may impact the detoxification of a variety of phenolic molecules in the host, which were previously thought to be solely detoxified via human sulfotransferases. However, further in vivo studies are necessary to understand potential contributions of ASSTs in host detoxification processes.

biochemistry↗