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Tanzillo, A.

Publications and source records attributed to Tanzillo, A..

2 recordsLinked to original sources
bioRxiv2025

Mature interneuron subtypes arise from distinct spatial and temporal subdomains within the caudal ganglionic eminence

Forebrain inhibitory interneurons are born from transient structures during embryogenesis known as the medial and caudal ganglionic eminences (MGE and CGE, respectively). The MGE and CGE generate distinct, non-overlapping cohorts of interneurons that can be defined by their transcriptomic, morphological, and electrophysiological characteristics. In the MGE, somatostatin-expressing (SST+) cells arise predominantly from the dorsal-posterior MGE from E12-E16 whereas parvalbumin-expressing (PV+) cells are born in the ventral-anterior MGE throughout embryogenesis. This relationship between spatiotemporal origin and mature interneuron subtypes has led to genetic insights regarding fate and maturation of these MGE-derived cells. A similar organization has never been explored in the CGE, despite the significant increase in CGE-derived interneurons in primates compared to rodents. Here we harvested fluorescent cells from distinct CGE subdomains at E13.5 and E15.5 and grafted them into WT neonatal mice cortices. One month post-transplantation, brains were immunostained for interneuron markers to relate mature CGE-derived interneurons with spatiotemporal origins within the CGE. Our results indicate that there are significant spatial biases in the CGE, with specific interneuron subtypes preferentially arising from distinct CGE subdomains. These biases are relatively stable over time, implying a minimal relationship between temporal birthdate and interneuron subtype. In the future, combining these insights with spatial transcriptome profiles will generate critical insights into gene regulation of CGE-derived interneurons.

neuroscience↗
bioRxiv2025

Reducing methylation of histone 3.3 lysine 4 in the medial ganglionic eminence and hypothalamus recapitulates neurodevelopmental disorder phenotypes

Methylation of lysine 4 on histone H3 (H3K4) is enriched on active promoters and enhancers and correlates with gene activation. Disruption of H3K4 methylation is associated with numerous neurodevelopmental diseases (NDDs) that display intellectual disability and abnormal body growth. Here, we perturb H3K4 methylation in the medial ganglionic eminence (MGE) and the hypothalamus, two brain regions associated with these disease phenotypes. These mutant mice have fewer forebrain interneurons, deficient network rhythmogenesis, and increased spontaneous seizures and seizure susceptibility. Mutant mice are significantly smaller than control littermates, but they eventually became obese due to striking changes in the genetic and cellular hypothalamus environment in these mice. Perturbation of H3K4 methylation in these cells produces deficits in numerous NDD-associated behaviors, with a bias for more severe phenotypes in female mice. Single cell sequencing reveals transcriptional changes in the embryonic and adult brain that underlie many of these phenotypes. In sum, our findings highlight the critical role of H3K4 methylation in regulating survival and cell-specific gene regulatory mechanisms in forebrain GABAergic and hypothalamic cells during neurodevelopment to control network excitability and body size homoeostasis.

neuroscience↗