Biology subjects

Conrad, A.

Publications and source records attributed to Conrad, A..

4 recordsLinked to original sources

bioRxiv2024

Glucocorticoids target postnatal oligodendrocyte precursor cells to modulate adult hippocampal network plasticity and stress-induced behavior

Glucocorticoid receptors (GRs) are key mediators of how the stress hormone glucocorticoids (GCs) shape postnatal brain development and adaptive plasticity. Because GC signaling is critical during this period, postnatal GC concentrations are tightly regulated in the brain, whereas excessive levels of circulating GCs can disrupt developmental trajectories and increase the risk of psychiatric disorders later in life. GR function influences multiple neural cell types, but its cell-specific roles, particularly early in development, remain poorly understood. Oligodendrocyte precursor cells (OPCs), which generate myelinating oligodendrocytes and actively modulate neuronal networks, express GRs and can therefore respond to fluctuations in GC levels. Although excessive GC exposure during early life adversity has been linked to changes in OPC development, the physiological role of GR signaling specifically within OPCs remains unclear. To address this, we conditionally deleted GRs in postnatal OPCs in mice to investigate the role of physiological GC signaling in OPC proliferation and maturation, as well as in neuronal network activity and behavior. This deletion resulted in reduced oligodendrocyte and myelinated axon density in the hippocampus, sex-specific alterations in hippocampal activity and long-term potentiation following acute challenge, and impairments in memory formation in adulthood. Our findings reveal a novel, OPC-specific role for GRs and suggest that physiological GR activity in the oligodendrocyte lineage contributes to normal hippocampal plasticity, learning and memory. Significance StatementGlucocorticoid receptors (GRs) mediate the effects of the stress hormone glucocorticoids (GCs) on postnatal brain development and adaptive plasticity. While the function of GRs in neurons is well characterized, much less is known about their role in oligodendrocyte precursor cells (OPCs). OPCs, which give rise to myelinating oligodendrocytes and participate in the modulation of neuronal networks, express GRs and can therefore sense fluctuations in GCs during stress response; however, the physiological role of GRs in OPCs remains unclear. In this study, we found that deleting GRs in early postnatal OPCs reduced the density of oligodendrocytes and of myelinated axons, altered hippocampal activity and long-term potentiation in response to acute challenge, and impaired memory formation in adult mice. These findings identify OPCs as key targets of GR signaling and suggest that physiological receptor activity in the oligodendrocyte lineage contributes to normal hippocampal plasticity, learning, and memory.

neuroscience↗

bioRxiv2023

Effects of ocean acidification on red king crab larval survival and development

Ocean acidification, a decrease in oceanic pH resulting from the uptake of anthropogenic CO2, can be a significant stressor for marine organisms. In this study, we reared red king crab larvae from hatching to the first crab stage in four different pH treatments: current surface ambient, diel fluctuation to mimic larval migration between the surface and mixed layer under current ambient conditions, pH 7.8, and pH 7.5. Larvae were monitored throughout development and the average length of each stage was determined. At each of the zoeal stages, the glaucothoe stage, and the first crab stage, we measured survival, morphometry, dry mass, and carbon, nitrogen, calcium, and magnesium content. Red king crab larvae were highly resilient to ocean acidification. There were no differences among treatments in survival or in average stage length. Although there were clear ontogenetic trends in size, weight, and elemental composition, most of these did not vary with pH treatment. Zoeal morphology did not vary among treatments, although glaucothoe and C1 crabs were slightly smaller in pH 7.8 than in the ambient treatment. Ambient larvae also had a slightly higher mass than pH 7.8 larvae but not pH 7.5. Ambient larvae had higher magnesium contents than pH 7.8 and pH 7.5, but calcium levels were the same. Ambient larvae also had slightly lower carbon and nitrogen content than pH 7.8 and pH 7.5 larvae but only in the 4th zoeal stage. Overall this study suggests that red king crab larvae are well adapted to a wide range of pH conditions and are unlikely to be significantly affected by ocean acidification levels projected for the next two centuries.

ecology↗

bioRxiv2022

Chimeric 3D-gastruloids - a versatile tool for studies of mammalian peri-gastrulation development

Stem cell-derived 3D-gastruloids show a remarkable capacity of self-organisation and recapitulate many aspects of gastrulation stage mammalian development. Gastruloids can be rapidly generated and offer several experimental advantages, such as scalability, observability, and accessibility for manipulation. Here, we present approaches to further expand the experimental potency of murine 3D-gastruloids by utilizing functional genetics in mouse embryonic stem cells (mESCs) to generate chimeric gastruloids. In chimeric gastruloids fluorescently labelled cells of different genotypes harbouring inducible gene-expression, or loss-of-function alleles, are combined with wildtype cells. We showcase this experimental approach in chimeric gastruloids of mESCs carrying homozygous deletions of the Tbx transcription factors Brachyury, or inducible expression of Eomes. Resulting chimeric gastruloids recapitulate reported Eomes and Brachyury functions, such as instructing cardiac fate and promoting posterior axial extension, respectively. Additionally, chimeric gastruloids revealed previously unrecognized phenotypes such as tissue sorting preference of Brachyury-deficient cells to endoderm, and cell non-autonomous effects of Brachyury-deficiency on Wnt3a-patterning along the embryonic axis, demonstrating some of the advantages of chimeric gastruloids as efficient tool for studies of mammalian gastrulation.

developmental biology↗

bioRxiv2019

The Chinese chestnut genome: a reference for species restoration

Forest tree species are increasingly subject to severe mortalities from exotic pests, diseases, and invasive organisms, accelerated by climate change. Forest health issues are threatening multiple species and ecosystem sustainability globally. While sources of resistance may be available in related species, or among surviving trees, introgression of resistance genes into threatened tree species in reasonable time frames requires genome-wide breeding tools. Asian species of chestnut (Castanea spp.) are being employed as donors of disease resistance genes to restore native chestnut species in North America and Europe. To aid in the restoration of threatened chestnut species, we present the assembly of a reference genome with chromosome-scale sequences for Chinese chestnut (C. mollissima), the disease-resistance donor for American chestnut restoration. We also demonstrate the value of the genome as a platform for research and species restoration, including new insights into the evolution of blight resistance in Asian chestnut species, the locations in the genome of ecologically important signatures of selection differentiating American chestnut from Chinese chestnut, the identification of candidate genes for disease resistance, and preliminary comparisons of genome organization with related species.

genomics↗