Biology subjects

Treichel, A. J.

Publications and source records attributed to Treichel, A. J..

3 recordsLinked to original sources

bioRxiv2024

Synaptic vesicle release regulates pre-myelinating oligodendrocyte-axon interactions in a neuron subtype-specific manner

Oligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron-glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific.

neuroscience↗

bioRxiv2020

A Genetic Model Therapy Proposes a Critical Role for Liver Dysfunction in Mitochondrial Biology and Disease

The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Here we present a new animal model that recapitulates key components of Leigh Syndrome, French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the Leucine Rich Pentatricopeptide repeat-containing motif (LRPPRC) gene. LRPPRC has native functions related to mitochondrial mRNA polyadenylation and translation as well as a role in gluconeogenesis. We used the Gene-Breaking Transposon (GBT) cassette to create a revertible, insertional mutant zebrafish line in the LRPPRC gene. lrpprc zebrafish homozygous mutants displayed impaired muscle development, liver function and lowered levels of mtDNA transcripts and are lethal by 12dpf, all outcomes similar to clinical phenotypes observed in patients. Investigations using an in vivo lipidomics approach demonstrated accumulation of non-polar lipids in these animals. Transcript profiling of the mutants revealed dysregulation of clinically important nuclearly encoded and mitochondrial transcripts. Using engineered liver-specific rescue as a genetic model therapy, we demonstrate survival past the initial larval lethality, as well as restored normal gut development, mitochondrial morphology and triglyceride levels functionally demonstrating a critical role for the liver in the pathophysiology of this model of mitochondrial disease. Understanding the molecular mechanism of the liver-mediated genetic rescue underscores the potential to improve the clinical diagnostic and therapeutic developments for patients suffering from these devastating disorders.

genetics↗

bioRxiv2019

Individual neuronal subtypes control initial myelin sheath growth and stabilization

BackgroundIn the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors.\n\nMethodsTo address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes.\n\nResultsIn the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons.\n\nConclusionWe conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

neuroscience↗