About

Christopher Deppmann is a Professor of Biology at the University of Virginia. His research interests focus on the mechanisms governing nervous system assembly and disassembly, with particular attention to peripheral nervous system development. His lab investigates various aspects such as competition for survival, synapse formation and restriction, and how antagonistic cytokine signaling influences nervous system construction and refinement. Deppmann's work includes exploring the molecular basis of long-distance neurotrophic signaling and how TNFR family signaling suppresses pro-growth cues to promote nervous system refinement. In collaboration with other labs, his group develops non-invasive tools to better understand neural circuit assembly and function. Additionally, his research applies insights from nervous system development to address nervous system pathology related to degeneration, pain, and metabolism.

Research topics

• Biology
• Neuroscience
• Internal medicine
• Endocrinology
• Medicine
• Immunology
• Cell biology
• Cancer research
• Chemistry
• Biochemistry

Selected publications

• Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS.

  DZNE Pub · 2026-01-01

  articleOpen accessSenior author
  Publisher

• Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS

  Neurobiology of Disease · 2026-01-10

  articleOpen access

  Mutations in FUSED IN SARCOMA (FUS ) cause juvenile-onset amyotrophic lateral sclerosis (ALS). Early pathogenesis of FUS-ALS involves impaired transcription and splicing, DNA damage response, and axonal degeneration. However, the molecular pathophysiology and the link between somatic and axonal phenotypes are still poorly understood. We evaluated whether compartment-specific transcriptome differences could distinguish and drive early axonal degeneration. We used iPSC-derived motor neurons (MNs) coupled with microfluidic approaches to generate RNA-sequencing profiles from axonal and somatodendritic compartments. We demonstrate that the axonal transcriptome is unique and distinct, with RNA metabolism, extracellular secretion, and matrix disassembly pathways particularly enriched in distal axonal compartments. FUS mutation leads to changes in distinct pathways that were clustered in only a few distinct protein-protein interaction (PPI) networks. Somatodendritic changes upon FUS mutation include WNT signaling, mitochondrial, extracellular matrix (ECM)-, and synapse-related functions. In contrast, analysis of the axonal transcriptome in mutant MNs centers on the PLK1 pathway, mitochondrial gene expression, and regulation of inflammation. Comparison to CLIP-seq data revealed a significant enrichment for PLK1 and DNA replication pathways in axons. PLK1 upregulation did not activate cell-cycle re-entry but contributed to mutant MN survival, and its inhibition increased neuronal cell death. We propose that upregulation of PLK1 represents an early event in the pathogenesis of ALS and could act in response to DNA damage, mitochondrial damage, and immune response activation in the affected cells. Additionally, downregulation of ECM pathways in the somatodendritic compartment and axons could explain strongly compromised dynamics of axonal outgrowth. Overall, we provide a novel valuable resource of the potential targets and affected processes changed in the specific compartments of FUS-ALS motoneurons. • Compartment-specific transcriptomics of FUS-P525L MNs reveal ALS-relevant changes. • WNT, mitochondrial and synaptic pathways are altered in somatodendritic compartment of ALS MNs. • PLK1, mitochondrial, inflammatory, and ECM pathways are dysregulated in axons. • CLIP-seq data revealed a nearly exclusive enrichment for PLK1 and DNA replication pathways in axons. • PLK1 upregulation promotes survival of FUS-P525L mutant motoneurons.

  PublisherDOI

• A Single-Cell Signaling Atlas of Spinal Cord BDNF Responses Reveals Determinants Beyond Receptor Expression

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-27

  articleOpen accessSenior author

  Abstract Although the influence of Brain-Derived Neurotrophic Factor (BDNF) has been characterized across numerous neural settings, how individual cells decode this pleiotropic message into context-dependent signaling responses remains unresolved. Using highly multiplexed single-cell mass cytometry to simultaneously measure levels of 19 signaling markers and 18 cell ID markers, we constructed a temporal atlas of BDNF-induced signaling relative to two control conditions across diverse spinal cord lineages and maturation states. We demonstrate that not all cells contribute to the global BDNF response with ∼47-75% of cells having increased ERK phosphorylation at peak activation. Our analysis of 20 uniquely identified cell identities reveals that TrkB/p75NTR receptor stoichiometry sets the potential for response, but ultimately the sustained reduction of surface TrkB predicts BDNF sensitivity. Surprisingly, identical receptor profiles in distinct cell types yield fundamentally different signaling responses, indicating that cell identity acts as the final arbiter of the BDNF message. These findings reframe BDNF sensitivity as a form of prepared competence. This work thus provides a framework for understanding how intracellular context dictates the functional interpretation of neurotrophic cues.

  PublisherDOI

• A brain reward circuit inhibited by next-generation weight-loss drugs in mice

  Nature · 2026-05-06

  articleOpen access

  Glucagon-like peptide 1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes; however, established peptide-based therapies require injections and are complex to manufacture1–3. Small-molecule GLP1RAs promise oral bioavailability and scalable manufacturing, but their selective binding to human versus rodent receptors has limited mechanistic studies4–9. Here we developed humanized GLP1R mouse models to investigate how small-molecule GLP1RAs influence feeding behaviour. We found that these compounds regulate both homeostatic and hedonic feeding through parallel neural circuits. Beyond engaging canonical hypothalamic and hindbrain networks that control metabolic homeostasis, GLP1RAs recruit a discrete population of Glp1r-expressing neurons in the central amygdala, which selectively suppress the consumption of palatable foods by reducing dopamine release in the nucleus accumbens. Stimulating these central amygdalar neurons curtails hedonic feeding, whereas targeted deletion of the receptor in this cell population specifically diminishes the anorectic efficacy of GLP1RAs for reward-driven intake. These findings identify a neural circuit through which small-molecule GLP1RAs modulate reward processing, with implications for the treatment of substance-use disorder and binge eating. Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implications for how these orally delivered weight-loss drugs engage brain reward circuits.

  PublisherDOI

• Extrinsic Apoptosis and Necroptosis in Telencephalic Development: A Single-Cell Mass Cytometry Study

  Research Square · 2025-03-24

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Axonal spheroids are regulated by Schwann cells after peripheral nerve injury

  Glial health research. · 2025-03-12

  articleOpen accessSenior authorCorresponding

  Axonal spheroids are hallmark features of neurodegeneration, forming along degenerating axons and contributing to disease progression. Despite their ubiquity across degenerative etiologies, the dynamics of spheroid disappearance, as well as their interactions with glial cells, remain poorly understood. Here, using an in vivo zebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells. These results describe spheroid dynamics across their lifetimes, establish a role for the extra-axonal environment in altering spheroid outcomes, and identify a cellular mechanism whereby spheroid fates are altered. • Axonal spheroids (also called “dystrophic neurites,” “axonal swellings,” and “axonal beading”) undergo three fates: shrinking, breakdown, and uniform disappearance • Schwann cells ensheath most axonal spheroids and internalize a subset of them • Schwann cells regulate axonal spheroid fates, identifying a role for axon-extrinsic processes in spheroid regulation

  PublisherDOI

• BDNF receptor balance gates AgRP-to-PVH fiber density and stimulation-evoked feeding across caloric states

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-17

  preprintOpen accessSenior authorCorresponding

  Abstract Agouti-related peptide (AgRP) neurons show opposite pairings of anatomy and output across caloric states. In mice, 24-h caloric restriction (CR) increases AgRP-to-paraventricular hypothalamus (PVH) fiber density without increasing stimulation-evoked feeding, whereas 5-day high-fat diet (HFD) reduces fiber density yet increases stimulation-evoked feeding, including during PVH terminal stimulation. PVH Bdnf rises acutely under both challenges and remains elevated with sustained HFD. Receptor expression shifts with state: in AgRP neurons, CR increases TrkB transcripts, whereas HFD increases p75NTR transcripts. AgRP-specific deletions define directional roles: TrkB loss reduces AgRP-to-PVH fiber density and yields larger stimulation-evoked feeding, whereas p75NTR loss increases fiber density and limits responses. Thus, a TrkB/p75NTR balance in AgRP neurons provides rheostat-like control over the relationship between circuit structure and stimulation-evoked feeding across caloric states, identifying TrkB and p75NTR as tractable molecular handles for probing state-dependent control of AgRP circuit output. Highlights CR increases AgRP→PVH fibers without boosting evoked feeding HFD retracts AgRP→PVH fibers and amplifies evoked feeding PVH Bdnf rises acutely in response to CR or HFD; elevation persists only with HFD AgRP TrkB ↑ with CR, p75NTR ↑ with HFD; AgRP specific knockouts of these receptors define floor and ceiling PVH axon innervation/evoked feeding

  PublisherOA PDFDOI

• Extrinsic Apoptosis and Necroptosis in Telencephalic Development: A Single-Cell Mass Cytometry Study

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-04

  preprintOpen accessSenior authorCorresponding

  Regulated cell death is integral to sculpting the developing brain, yet the relative contributions of extrinsic apoptosis and necroptosis remain unclear. Here, we leverage single-cell mass cytometry (CyTOF) to characterize the cellular landscape of the mouse telencephalon in wild-type (WT), RIPK3 knockout (RIPK3 KO), and RIPK3/Caspase-8 double knockout (DKO) mice. Strikingly, combined deletion of RIPK3 and Caspase-8 leads to a 12.6% increase in total cell count, challenging the prevailing notion that intrinsic apoptosis exclusively governs developmental cell elimination. Detailed subpopulation analysis reveals that DKO mice display selective enrichment of Tbr2⁺ intermediate progenitors and endothelial cells, underscoring distinct, cell type-specific roles for extrinsic apoptotic and necroptotic pathways. These findings provide a revised framework for understanding the coordinated regulation of cell number during telencephalic development and suggest potential mechanistic links to neurodevelopmental disorders characterized by aberrant cell death.

  PublisherOA PDFDOI

• Characterizing Microglial Signaling Dynamics During Inflammation Using Single‐Cell Mass Cytometry

  Glia · 2025-01-08 · 4 citations

  articleOpen accessSenior authorCorresponding

  Microglia play a critical role in maintaining central nervous system (CNS) homeostasis and display remarkable plasticity in their response to inflammatory stimuli. However, the specific signaling profiles that microglia adopt during such challenges remain incompletely understood. Traditional transcriptomic approaches provide valuable insights, but fail to capture dynamic post-translational changes. In this study, we utilized time-resolved single-cell mass cytometry (CyTOF) to measure distinct signaling pathways activated in microglia upon exposure to bacterial and viral mimetics-lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (Poly(I:C)), respectively. Furthermore, we evaluated the immunomodulatory role of astrocytes on microglial signaling in mixed cultures. Microglia or mixed cultures derived from neonatal mice were treated with LPS or Poly(I:C) for 48 h. Cultures were stained with a panel of 33 metal-conjugated antibodies targeting signaling and identity markers. High-dimensional clustering analysis was used to identify emergent signaling modules. We found that LPS treatment led to more robust early activation of pp38, pERK, pRSK, and pCREB compared to Poly(I:C). Despite these differences, both LPS and Poly(I:C) upregulated the classical reactivity markers CD40 and CD86 at later time points. Strikingly, the presence of astrocytes significantly blunted microglial responses to both stimuli, particularly dampening CD40 upregulation. Our studies demonstrate that single-cell mass cytometry effectively captures the dynamic signaling landscape of microglia under pro-inflammatory conditions. This approach may pave the way for targeted therapeutic investigations of various neuroinflammatory disorders. Moreover, our findings underscore the necessity of considering cellular context, such as astrocyte presence, in interpreting microglial behavior during inflammation.

  PublisherOA PDFDOI

• Extrinsic apoptosis and necroptosis in telencephalic development: a single-cell mass cytometry study

  Cell Death and Differentiation · 2025-10-21 · 1 citations

  articleOpen accessSenior authorCorresponding

  Regulated cell death is integral to sculpting the developing brain, yet the relative contributions of extrinsic apoptosis and necroptosis remain unclear. Here, we leverage single-cell mass cytometry (CyTOF) to characterize the cellular landscape of the mouse telencephalon in wild-type (WT), RIPK3 knockout (RIPK3 KO), and RIPK3/Caspase-8 double knockout (DKO) mice. Strikingly, combined deletion of RIPK3 and Caspase-8 leads to a 12.6% increase in total cell count, challenging the prevailing notion that intrinsic apoptosis exclusively governs developmental cell elimination. Detailed subpopulation analysis reveals that DKO mice display selective enrichment of Tbr2⁺ intermediate progenitors and endothelial cells, underscoring distinct, cell type-specific roles for extrinsic apoptotic and necroptotic pathways. These findings provide a revised framework for understanding the coordinated regulation of cell number during telencephalic development and suggest potential mechanistic links to neurodevelopmental disorders characterized by aberrant cell death.

  PublisherOA PDFDOI

Recent grants

• Extrinsic Mechanisms Governing Injury-Induced Axon Degeneration

  NIH · $4.0M · 2015–2026

• NIH Grant R01NS072388

  NIH · $1.7M · 2017

• NIH Grant F32NS053187

  NIH · $151k · 2008

• CAREER: Emergent Properties of Systems Matching in Peripheral Nervous System Development

  NSF · $900k · 2015–2020

Frequent coauthors

• David D. Ginty

  Harvard University

  24 shared

• Nikhil Sharma

  24 shared

• Kanchana K. Gamage

  23 shared

• Bonnie E. Lonze

  New York University

  20 shared

• Ştefan Mihalaş

  17 shared

• Anthony Spano

  University of Minnesota

  15 shared

• Austin B. Keeler

  13 shared

• Ernst Niebur

  Italian Institute of Technology

  12 shared