Biology subjects

Saint-Martin, M.

Publications and source records attributed to Saint-Martin, M..

3 recordsLinked to original sources

bioRxiv2026

Hindbrain explants enable multimodal and longitudinal analysis of the developing olivo-cerebellar circuit at single-cell resolution

Experimental models that preserve native mammalian CNS circuitry while enabling longitudinal analysis of circuit assembly at single-cell resolution remain scarce, limiting mechanistic studies and therapeutic discovery. Here, we establish embryonic mouse hindbrain explants as a scalable in vitro model that maintains the long-range olivo-cerebellar circuit while providing direct experimental access to both pre- and postsynaptic neurons. The preparation supports repeated live imaging, targeted single-cell manipulation and labelling, electrophysiology, ultrastructural analysis, and single-cell RNA sequencing during circuit assembly. Hindbrain explants faithfully recapitulate key features of olivo-cerebellar organization and development, including cytoarchitecture, synaptic organization and maturation, neuronal differentiation, and spontaneous network activity while preserving developmental glial features. By combining developmental and physiological fidelity with longitudinal multimodal accessibility, this resource bridges the gap between reductionist cultures and technically demanding in vivo approaches, providing a versatile and ethical model for investigating the molecular and cellular mechanisms of cerebellar circuit assembly and disease.

neuroscience↗

bioRxiv2025

Evolutionary rescue and adaptive reversal allowed the persistence of freshwater copepods during historical lake acidification and pH recovery

The persistence of populations facing severe environmental disturbance can be enabled by natural selection on heritable phenotypic variation - a process known as evolutionary rescue. Few studies have documented this process in complex natural settings and the long-term outcome of evolutionary rescue. Here, we used copepod resting eggs of Leptodiaptomus minutus from three time periods of lake ecological history, spanning {approx} 200 generations (100 years) in two populations impacted by historical acidification. Whole genome sequencing of the resting eggs revealed significant allele frequency shifts associated with the acidification followed by pH recovery. We used a resurrection ecology approach to retrace adaptive shifts concomitant with environmental transitions. Copepods from the pre-acidification period showed sensitivity to acidity, while individuals from the acidification period were adapted to acidic pH. This tolerance was subsequently lost during pH recovery, implying an adaptive reversal. Demographic models indicated a decline during the acidification process followed by population recovery based on historical data, suggesting that selection led to evolutionary rescue. This study fills a critical knowledge gap about the long-term implications of evolutionary rescue in the wild.

evolutionary biology↗

bioRxiv2023

A role for APP in the development of astrocyte morphological complexity

The amyloid precursor protein (APP), whose proteolytic cleavage gives rise to amyloid-{beta} peptide, has been extensively studied for its role in Alzheimers disease, but its physiological function remains less understood. In neurons, APP and its two homologs, the amyloid precursor-like protein 1 (APLP1) and 2 (APLP2), are present in the synaptic compartment and promote synaptogenesis. Over recent years, astrocytes, an abundant glial cell in the brain, have attracted much attention for their role in regulating synapse formation and function. Although APP is also found in astrocytes, its role in these cells remains largely unexplored. Here we have sought to investigate the expression and function of APP in rodent astrocytes in vitro and in vivo. We find that APP along with its family members, APLP1 and APLP2, are expressed in astrocytes in vitro and in vivo. In primary hippocampal cultures, shRNA-mediated knockdown of astrocytic APP, APLP1 or APLP2 compromises astrocyte morphological elaboration to varying degrees. We have then focused on APP to characterize its role in astrocyte development in the intact brain. We show that astrocytic APP shapes the morphological complexity of astrocyte processes in vivo and may also modulate postsynaptic assembly. Our results highlight a role of astrocytic APP and possibly of APLPs that could potentially impact neuronal functions.

neuroscience↗