Biology subjects

Gaspari, S.

Publications and source records attributed to Gaspari, S..

4 recordsLinked to original sources

bioRxiv2026

LightSuite: scalable atlas registration and cell detection across the central nervous system

Deciphering brain-wide circuits requires large animal cohorts, yet computational bottlenecks in atlas registration and whole-volume cell detection reduce precision, reproducibility, and sample yield. We present LightSuite, an open-source framework enabling scalable, multimodal registration and cellular mapping across the central nervous system (CNS). LightSuite combines damage-resilient 3D point-cloud initialization with user-steerable non-rigid registration, and GPU-accelerated local background normalization for rapid, illumination-invariant cell detection. Applying LightSuite to Fos-dependent activity labeling in mice, we extracted reproducible, layer-resolved profiles of active cell density, soma-size distributions and per-animal labeling-efficiency factors. LightSuite computationally untwists and registers cleared spinal cords to map myeloarchitecture, reconstructs serial wide-field histology to map surface GluA1 distributions, resolves optic fiber tracks, and aligns in vivo functional ultrasound hemodynamics into common atlas coordinates. LightSuite establishes an integrated, accessible platform for cohort-level structural, molecular, and functional CNS mapping.

neuroscience↗

bioRxiv2025

Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links myelin homeostasis to counterregulation and metabolic health.

The counterregulatory response (CRR) to hypoglycemia is a fundamental, evolutionarily conserved homeostatic mechanism orchestrated by the central nervous system (CNS) to ensure survival during glucose scarcity. In individuals with diabetes, this response is frequently impaired, contributing to life-threatening episodes of hypoglycemia. Tmem117 was previously identified in a genetic screen as a promising hypothalamic regulator of CRR. Our previous work highlighted its contribution to CRR through regulation of vasopressin secretion. Here, we reveal that Tmem117 is also enriched in cells of the oligodendrocytic lineage and we characterize the contribution of oligodendrocytic Tmem117 in CRR. We show that depletion of Tmem117 from either all oligodendrocyte lineage cells or only mature oligodendrocytes leads to myelin deficits and male-specific defects in CRR. Furthermore, we reveal that transient, adult-onset depletion of Tmem117 in mature oligodendrocytes is sufficient to induce long-lasting metabolic imbalances in male mice, suggesting that defects in oligodendrocytes and myelin can affect peripheral glucose homeostasis. Mechanistically, we provide for the first-time insights on the function of Tmem117 showing that it regulates intracellular calcium dynamics through its interaction with the sodium-calcium exchanger NCX1. Together, these results redefine our understanding of the cellular contributors to the CRR, highlight the importance of oligodendrocytes in systemic glucose regulation, and position Tmem117 as a promising molecular target for cell-specific manipulation of NCX activity.

neuroscience↗

bioRxiv2022

Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia

The counterregulatory response to hypoglycemia (CRR), which ensures a sufficient glucose supply to the brain, is an essential survival function. It is orchestrated by incompletely characterized glucose-sensing neurons, which trigger a coordinated autonomous and hormonal response that restores normoglycemia. Here, we investigated the role of hypothalamic Tmem117, identified in a genetic screen as a regulator of CRR. We show that Tmem117 is expressed in vasopressin magnocellular neurons of the hypothalamus. Tmem117 inactivation in these neurons increases hypoglycemia-induced vasopressin secretion leading to higher glucagon secretion, an estrus cycle phase-dependent effect in female mice. Ex vivo electrophysiological analysis, in-situ hybridization and in vivo calcium imaging reveal that Tmem117 inactivation does not affect the glucose-sensing properties of vasopressin neurons but increases ER-stress, ROS production and intracellular calcium levels accompanied by increased AVP production and secretion. Thus, Tmem117 in vasopressin neurons is a physiological regulator of glucagon secretion and highlight the role of these neurons in the coordinated response to hypoglycemia.

physiology↗

bioRxiv2022

A novel Smg6 mouse model reveals regulation of circadian period and daily CRY2 accumulation through the nonsense-mediated mRNA decay pathway

Nonsense-mediated mRNA decay (NMD) has been intensively studied as a surveillance pathway that degrades erroneous transcripts arising from mutations or RNA processing errors. While additional roles in controlling regular mRNA stability have emerged, possible functions in mammalian physiology in vivo have remained unclear. Here, we report a novel conditional mouse allele that allows converting the NMD effector nuclease SMG6 from wild-type to nuclease domain-mutant protein. We analyzed how NMD downregulation affects the function of the circadian clock, a system known to require rapid mRNA turnover. We uncover strong lengthening of free-running circadian periods for liver and fibroblast clocks, and direct NMD regulation of Cry2 mRNA, encoding a key transcriptional repressor within the rhythm-generating feedback loop. In the entrained livers of Smg6 mutant animals we reveal transcriptome-wide alterations in daily mRNA accumulation patterns, altogether expanding the known scope of NMD regulation in mammalian gene expression and physiology.

genetics↗