Biology subjects

Rust, K.

Publications and source records attributed to Rust, K..

7 recordsLinked to original sources

bioRxiv2026

Intrasegmental and propriospinal pre-phrenic interneuron circuitry in intact CNS and following cervical spinal cord injury

Cervical spinal cord injury (SCI) disrupts descending respiratory circuitry, resulting in debilitating and often persistent ventilatory deficits. Respiratory drive emerges within medulla from the rostral ventral respiratory group (rVRG), whose neurons project to C3-C6 phrenic motor neurons (PhMNs), which then innervate diaphragm, the primary muscle of inspiration. Though rVRG neurons make extensive monosynaptic connection with PhMNs, rVRG input to PhMNs can also be relayed through pre-phrenic interneurons (PP-INs) via polysynaptic pathways. However, the neuroanatomical connectivity between PP-INs and PhMNs remains incompletely understood. In both uninjured rats and the C2 hemisection (C2HS) model of cervical SCI, we performed tracing of PP-INs that were synaptically connected to PhMNs located in rostral (C3-C4) or caudal (C5-C6) portions of the phrenic nucleus by unilaterally injecting retrograde trans-synaptic tracer, pseudorabies (PRV), selectively into ventral or dorsal regions of hemi-diaphragm. We quantified numbers of PRV-labeled PP-INs individually at segments across cervical spinal cord, including separately in dorsal horn, intermediate gray, and ventral horn. We found that PP-INs are widespread throughout C1-C7 spinal cord in the uninjured condition. These PP-INs have a predominant intrasegmental connectivity pattern with PhMNs, though significant numbers of longer distance projecting propriospinal PP-INs also exist both rostral and caudal to the PhMN pool. Furthermore, while PP-INs connect both ipsilaterally and contralaterally with PhMNs, there is a strong bias to ipsilateral projection. C2HS induced major disconnection between PhMNs and ipsilesional propriospinal PP-INs located rostral to the SCI, but conversely induced limited plasticity in connectivity of intrasegmental PP-INs located within C3-C6 spinal cord. These findings greatly improve our knowledge about PP-IN circuitry and also provide important information to aid in developing approaches to target PP-IN plasticity for promoting spinal cord repair.

neuroscience↗

bioRxiv2025

Independent signaling pathways provide a fail-safe mechanism to prevent tumorigenesis

Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here we use single-cell transcriptomics to investigate the effects of pro-proliferative signaling on epithelial homeostasis using the Drosophila follicle cell lineage. Notably, EGFR-Ras overactivation induces cell cycle defects by activating the transcription factors Pointed and E2f1 and impedes differentiation. Hh signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of EMT-associated transcription factors zfh1 and Mef2. As a result, overactivation of Hh signaling generates a transcriptional hybrid state comparable to epithelial-mesenchymal-transition. Co-overactivation of Hh signaling with EGFR-Ras signaling blocks differentiation and induces key characteristics of tumor cells including a loss of tissue architecture caused by reduced expression of cell adhesion molecules, sustained proliferation and an evasion of cell cycle checkpoints. These findings provide new insight into how non-interacting signaling pathways converge at the transcriptional level to prevent malignant cell behavior. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/640798v2_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@762724org.highwire.dtl.DTLVardef@103d1a6org.highwire.dtl.DTLVardef@1b90caforg.highwire.dtl.DTLVardef@1eff5a4_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Distinct Non-occluding Functions of Septate Junction Components in Signaling Pathway Regulation and Cell Polarity During Epithelial Development

Occluding junctions are essential for epithelial tissue integrity and barrier function but also exert non-occluding roles. Here we identify a several crucial function of the invertebrate occluding junction components Coracle, Nervana 2, Neurexin-IV, and Kune-kune in regulating cell polarity during follicle epithelium development. We show that the morphogenesis of the follicular stalk is an actin-driven process that requires intact apical-basal cell polarity, which is controlled by septate junction components. Occluding junction components further regulate signaling pathways in a cell-type specific manner. In undifferentiated stem cells and immediate daughters, septate junction components promote effective Wnt signaling to control proliferation, while they limit Jak-STAT signaling activity induced by polar cells. Together, our data emphasize the multiple roles of occluding junction components independent of their classical role in forming the paracellular barrier.

cell biology↗

bioRxiv2022

PSC niche develops into immune-responsive blood cells capable of transdifferentiating into lamellocytes in Drosophila

Drosophila blood cells called hemocytes form an efficient barrier against infections and tissue damage. During metamorphosis, hemocytes undergo tremendous changes in their shape and behavior preparing them for tissue clearance. Yet, the diversity and functional plasticity of pupal blood cells have not been explored. Here, we combine single-cell transcriptomics and high-resolution microscopy to dissect the heterogeneity and plasticity of pupal hemocytes. We identified precursor and effector hemocytes with distinct molecular signatures and cellular functions clearly distinct from other stages of hematopoiesis. Strikingly, we identified that PSC cells, which function as lymph gland niche, are highly migratory and immune responsive cells in the pupa. PSC cells can transdifferentiate to lamellocytes triggered by wasp infection. Altogether, our data highlight a remarkable cell heterogeneity, and identifies a cell population that acts not only as a stem cell niche in larval hematopoiesis, but functions as cell reservoir to pupal and adult blood cells.

cell biology↗

bioRxiv2022

Gabapentin Disrupts Binding of Perlecan to the α2δ1 Voltage Sensitive Calcium Channel Subunit and Impairs Skeletal Mechanosensation

Our understanding of how osteocytes, the principal mechanosensors within bone, sense and perceive force remains unclear. Previous work identified "tethering elements" (TEs) spanning the pericellular space of osteocytes and transmitting mechanical information into biochemical signals. While we identified the heparan sulfate proteoglycan perlecan (PLN) as a component of these TEs, PLN must attach to the cell surface to induce biochemical responses. As voltage-sensitive calcium channels (VSCCs) are critical for bone mechanotransduction, we hypothesized that PLN binds the extracellular 2{delta}1 subunit of VSCCs to couple the bone matrix to the osteocyte membrane. Here, we showed co-localization of PLN and 2{delta}1 along osteocyte dendritic processes. Additionally, we quantified the molecular interactions between 2{delta}1 and PLN domains and demonstrated for the first time that 2{delta}1 strongly associates with PLN via its domain III. Furthermore, 2{delta}1 is the binding site for the commonly used pain drug, gabapentin (GBP), which is associated with adverse skeletal effects when used chronically. We found that GBP disrupts PLN::2{delta}1 binding in vitro, and GBP treatment in vivo results in impaired bone mechanosensation. Our work identified a novel mechanosensory complex within osteocytes composed of PLN and 2{delta}1, necessary for bone force transmission and sensitive to the drug GBP. This work provides insights into the mechanisms underlying mechanotransduction and will inform future studies to understand the mechanisms responsible for the negative effects of GBP on bone.

molecular biology↗

bioRxiv2021

Fly Cell Atlas: a single-cell transcriptomic atlas of the adult fruit fly

The ability to obtain single cell transcriptomes for stable cell types and dynamic cell states is ushering in a new era for biology. We created the Tabula Drosophilae, a single cell atlas of the adult fruit fly which includes 580k cells from 15 individually dissected sexed tissues as well as the entire head and body. Over 100 researchers from the fly community contributed annotations to >250 distinct cell types across all tissues. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types that are shared between tissues, such as blood and muscle cells, allowed the discovery of rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the entire Drosophila community and serves as a comprehensive reference to study genetic perturbations and disease models at single cell resolution.

genomics↗

bioRxiv2019

A Single-Cell Atlas and Lineage Analysis of the Adult Drosophila Ovary

The Drosophila ovary is a widely used model for germ cell and somatic tissue biology. We have used single-cell RNA-sequencing to build a comprehensive cell atlas of the adult Drosophila ovary containing unique transcriptional profiles for every major cell type in the ovary, including the germline and follicle stem cells. Using this atlas we identify novel tools for identification and manipulation of known and novel cell types and perform lineage tracing to test cellular relationships of previously unknown cell types. By this we discovered a new form of cellular plasticity in which inner germarial sheath cells convert to follicle stem cells in response to starvation.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC=\"FIGDIR/small/798223v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (60K):\norg.highwire.dtl.DTLVardef@b4c486org.highwire.dtl.DTLVardef@1d24e4aorg.highwire.dtl.DTLVardef@1217adorg.highwire.dtl.DTLVardef@1d09a63_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗