Biology subjects

Schulz, D. J.

Publications and source records attributed to Schulz, D. J..

7 recordsLinked to original sources

bioRxiv2026

Neuronal Gene Architecture in Cancer borealis Revealed by Long-Read Genome Assembly and Deep Transcriptomic Analysis

Understanding the underlying neuronal function in non-model organisms requires accurate resolution of gene structure and transcript diversity. Here, we present a comprehensive genome annotation tor the Jonah crab (Cancer borealis), a key experimental system in crustacean neurobiology, with a particular focus on transcriptome-supported neuronal gene architecture. By integrating long-read genome assembly with extensive transcriptomic evidence, we reconstructed gene models with high confidence, enabling detailed characterization of exon-intron organization, alternative splicing, and isotorm diversity across gene families. Functional classification revealed extensive representation of neural-associated gene classes, including ion channels and receptors, transporters, enzymes, zinc finger proteins, histones, structural proteins, and cell adhesion molecules, alongside a large set of previously uncharacterized genes. In this study we particularly focused on the neuronal and ion channel gene families known to underlie circuit-level neuronal function in C. borealis. We provide an in-depth analysis of 87 genes spanning 17 neural-related gene families and 41 neuropeptides, detailing chromosomal localization, gene length, exon-intron configuration, and transcript-supported isotorm structure. For many of these genes, transcriptomic data confirmed expression and refined coding boundaries. Comparisons with existing transcriptomic datasets demonstrate strong concordance in gene expression patterns while also revealing novel transcripts and expanded gene family members not previously annotated. Together, this genome and transcriptome-integrated annotation establishes a high-resolution framework tor studying neuronal gene organization in C. borealis. T his resource enables direct connections between gene architecture, transcript diversity, and neural function, supporting future investigations in crustacean neurogenomics, comparative genomics, and the evolution of nervous system complexity.

genomics↗

bioRxiv2025

Effects of Experimental Autoimmune Encephalomyelitis on Bladder Function and Properties of Pelvic Ganglion Neurons

Multiple sclerosis (MS) has substantial impacts on autonomic function. In part, MS results in loss of normal autonomic activity that contributes to disease-associated pathology such as neurogenic bladder, bowel, and sexual dysfunction. Yet little is known of the impacts of MS on peripheral autonomic neurons that directly innervate these target organs. In this study, we measured changes in properties of neurons of the mouse major pelvic ganglion (MPG) associated with two different levels of severity in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. Our data show that bladder function and physiological properties of MPG neurons are altered in association with EAE, and differ between less and more severe clinical scores associated with disease progression. EAE results in decreased bladder function measured by decreased urine output and increased micturition pressures. In the most severely affected animals, action potentials (APs) in MPG neurons show increased half-widths as a result of decreased maximum decay slopes leading to overall broader and longer APs and lower maximum firing frequency. These changes in AP properties are associated with differences in ion channel subunit expression as well. KCNA1-4, KCNN3 and SCN2A1 and SCN3A mRNA levels in MPGs decreased with disease severity. Taken together, our data indicate that peripheral autonomic neurons are fundamentally altered in EAE, suggesting that longer-term therapeutic approaches for MS could target these neurons directly to potentially help ameliorate neurogenic target organ dysfunction.

neuroscience↗

bioRxiv2023

TREM2 limits necrotic core formation during atherogenesis by controlling macrophage survival and efferocytosis

Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries [1], [2], and its main complications, myocardial infarction and stroke, are the leading cause of mortality worldwide [3]. Recent studies have identified Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating several key myeloid cell functions [4], as a highly expressed marker of macrophage foam cells in experimental and human atherosclerosis [5]. However, the function of TREM2 in the development of atherosclerosis is unknown. Here, we show that hematopoietic or global TREM2 deficiency increases necrotic core formation in early experimental atherosclerosis. We further demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages, and to the survival of lipid-laden macrophages, altogether indicating a crucial role of TREM2 in maintaining the balance between foam cell death and their clearance in atherosclerotic lesions, thereby controlling plaque necrosis.

immunology↗

bioRxiv2021

Crustacean cardiac ganglion model reveals constraints on morphology and conductances

The crustacean cardiac ganglion (CG) network coordinates the rhythmic contractions of the heart muscle to control the circulation of blood. The network consists of 9 cells, 5 large motor cells (LC1-5) and 4 small endogenous pacemaker cells (SCs). We report a new three-compartmental biophysical model of an LC that is morphologically realistic and includes provision for inputs from the SCs via a gap-junction coupled spike-initiation-zone (SIZ) compartments. To determine physiologically viable LC models in this realistic configuration, maximal conductances in three compartments of an LC are determined by random sampling from a biologically-characterized 9D-parameter space, followed by a three-stage rejection protocol that checks for conformity with electrophysiological features from single cell traces. LC models that pass the single cell rejection protocol are then incorporated into a network model which is then used in a final rejection protocol stage. Using disparate experimental data, the study provides hitherto unknown structure-function insights related to the crustacean cardiac ganglion large cell, including predictions about morphology including the role of its SIZ, and the differential roles of active conductances in the three compartments. Further, we extend analyses of emergent conductance relationships and correlations in model neurons relative to their biological counterparts, allowing us to make inferences both with respect to the biological system as well as the implications of the ability to detect such relationships in populations of model neurons going forward.

neuroscience↗

bioRxiv2019

Time-resolved single-cell transcriptomics uncovers dynamics of cardiac neutrophil diversity in murine myocardial infarction

ObjectiveAfter myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they can promote both tissue healing and damage. Here, we investigated the dynamics of cardiac neutrophil heterogeneity after infarction.\n\nMethods and resultsWe employed single-cell transcriptomics (scRNA-seq) to investigate temporal neutrophil heterogeneity in the heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, neutrophils could be delineated into six distinct clusters with specific time-dependent patterning and proportions. While the majority of neutrophils at day 1 were characterized by high expression of chemokines (e.g. Cxcl3, Ccl6), and putative activity of transcriptional regulators involved in hypoxic response (Hif1a) and emergency granulopoiesis (Cebpb), two major subsets of Siglecfhi (enriched for e.g. Icam1 and Tnf) and Siglecflow (Slpi, Ifitm1) neutrophils were found at 3 and 5 days. Flow cytometry analysis confirmed the presence of LY6G+SIGLECFhi and LY6G+SIGLECFlow neutrophils in the heart from 3 days after infarction onwards. LY6G+SIGLECFhi neutrophils were absent from the bone marrow, blood and spleen, suggesting local acquisition of surface SIGLECF. Acquisition of the SIGLECFhi state was paralleled by features of neutrophil ageing and activation (ICAM1hiCXCR4hiCD49dhiCD62Llow). scRNA-seq of atherosclerotic aortas revealed two neutrophil subsets with gene expression patterns reminiscent of the major Siglecfhi and Siglecflow cardiac neutrophil subpopulations, revealing that these populations may be present across distinct contexts of cardiovascular inflammation.\n\nConclusionAltogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse ischemic heart at the single-cell level, and suggests that temporal neutrophil heterogeneity is in part driven by local transition to a SIGLECFhi state.

immunology↗

bioRxiv2018

Effects of chronic spinal cord injury on relationships among ion channel and receptor mRNAs in mouse lumbar spinal cord

Spinal cord injury (SCI) causes widespread changes in gene expression of the spinal cord, even in the undamaged spinal cord below the level of the lesion. Less is known about changes in the correlated expression of genes after SCI. We investigated gene co-expression networks among voltage-gated ion channel and neurotransmitter receptor mRNA levels using quantitative RT-PCR in longitudinal slices of the mouse lumbar spinal cord in control and chronic SCI animals. These longitudinal slices were made from the ventral surface of the cord, thus forming slices relatively enriched in motor neurons or interneurons. We performed absolute quantitation of mRNA copy number for 50 ion channel or receptor transcripts from each sample, and used multiple correlation analyses to detect patterns in correlated mRNA levels across all pairs of genes. The majority of channels and receptors changed in expression as a result of chronic SCI, but did so differently across slice levels. Furthermore, motor neuron enriched slices experienced an overall loss of correlated channel and receptor expression, while interneuron slices showed a dramatic increase in the number of positively correlated transcripts. These correlation profiles suggest that spinal cord injury induces distinct changes across cell types in the organization of gene co-expression networks for ion channels and transmitter receptors.

neuroscience↗

bioRxiv2018

Dopamine maintains network synchrony via direct modulation of gap junctions in the crustacean cardiac ganglion

Abstract The Large Cell (LC) motor neurons of the crab (C. borealis) cardiac ganglion have variable membrane conductance magnitudes even within the same individual, yet produce identical synchronized activity in the intact network. In our previous study (Lane et al., 2016) we blocked a subset of K+ conductances across LCs, resulting in loss of synchronous activity. In this study, we hypothesized that this same variability of conductances could make LCs vulnerable to desynchronization during neuromodulation. We exposed the LCs to serotonin (5HT) and dopamine (DA) while recording simultaneously from multiple LCs. Both amines had distinct excitatory effects on LC output, but only 5HT caused desynchronized output. We further determined that DA rapidly increased gap junctional conductance. Co-application of both amines induced 5HT-like output, but waveforms remained synchronized. Furthermore, DA prevented desynchronization induced by the K+ channel blocker tetraethylammonium (TEA), suggesting that dopaminergic modulation of electrical coupling plays a protective role in maintaining network synchrony.

neuroscience↗