Details for: CL0000679

Cell ID: CL0000679

Cell Name: glutamatergic neuron

Description: A neuron that is capable of some neurotansmission by glutamate secretion.

Selected Context(s): Overall

Gene Significance Landscape

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Score:
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Genes

Contexts:

Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for glutamatergic neuron within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for glutamatergic neuron. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for glutamatergic neuron. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for glutamatergic neuron. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

Maximum number of selected genes.
Select a context for the baseline cell.
Select a context for the target cell.
Target Cell for CSI:  glutamatergic neuron (CL0000679)

 Legend
Nodes (Genes):
 Query Gene
Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
 Very High
 High
 Medium
 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

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## Summary A [glutamatergic neuron](/details-cell/CL0000679) is a neuron that utilizes glutamate as its primary neurotransmitter for signaling. The provided data highlights a specific subtype of these neurons characterized by a unique and extensive repertoire of cell adhesion molecules, suggesting a primary role in establishing and maintaining highly specific neural circuits. Strikingly, the top marker gene by expression specificity, [LGALS14](/details-gene/56891), is a galectin predominantly known for its immunomodulatory function in the placenta ([Link](https://doi.org/10.1073/pnas.0903568106)), pointing towards potentially novel neuro-immune functions for this cell type. The molecular profile is further defined by high specificity for various G-protein coupled receptors, including the relaxin-3 receptor [RXFP3](/details-gene/51289) and the metabotropic glutamate receptor [GRM5](/details-gene/2915), indicating these neurons are key points for integrating diverse neuromodulatory signals with canonical glutamatergic transmission. ## Key Characteristics and Function **Overall**, the gene significance profile suggests this [glutamatergic neuron](/details-cell/CL0000679) is a highly specialized cell type defined by its complex molecular machinery for synaptic connectivity, signaling integration, and potentially, neuro-immune interaction. * **Synaptic Adhesion and Circuit Specification:** A large and diverse set of cell adhesion and guidance molecules are highly specific markers for this cell. This includes members of the CUB and Sushi multiple domains family ([CSMD1](/details-gene/64478), [CSMD3](/details-gene/114788)), protocadherins ([PCDHAC2](/details-gene/56134), [PCDHGB5](/details-gene/56101)), and other immunoglobulin superfamily members like [DSCAM](/details-gene/1826), [CNTNAP5](/details-gene/129684), and [KIRREL3](/details-gene/84623). This extensive toolkit suggests a critical role in mediating precise cell-cell recognition, dendritic arborization, and the formation of specific, stable synaptic circuits. This is further supported by high specificity for postsynaptic density proteins such as [DLGAP2](/details-gene/9228) and [LRRC7](/details-gene/57554). * **Diverse Receptor-Mediated Signaling:** These neurons are characterized by the specific expression of several key G protein-coupled receptors. The high specificity score for [GRM5](/details-gene/2915) confirms their identity as neurons that not only release glutamate but are also responsive to it via metabotropic pathways. The prominence of [RXFP3](/details-gene/51289), the receptor for the neuropeptide relaxin-3, suggests these cells integrate long-range modulatory signals from brainstem nuclei with local glutamatergic activity ([Link](https://doi.org/10.1074/jbc.m308995200)). Additional markers like the muscarinic acetylcholine receptor [CHRM2](/details-gene/1129) and the GABA-A receptor subunit [GABRB2](/details-gene/2561) indicate this neuron acts as an integration hub for multiple neurotransmitter systems. * **Regulation of Neuronal Excitability:** Specific ion channel and transporter expression contributes to a distinct electrophysiological profile. Key markers include the voltage-gated potassium channel subunit [KCND2](/details-gene/3751), which mediates transient outward currents critical for action potential repolarization, and the sodium/calcium exchanger [SLC24A2](/details-gene/25769), crucial for maintaining calcium homeostasis. * **Distinct Metabolic Profile:** The anti-markers provide insight into what this cell is not. The strong negative significance scores for numerous mitochondrially-encoded genes essential for the electron transport chain, such as [COX1](/details-gene/4512), [ATP6](/details-gene/4508), [COX2](/details-gene/4513), [CYTB](/details-gene/4519), and [COX3](/details-gene/4514), may suggest a specialized metabolic state with lower reliance on oxidative phosphorylation compared to the average cell type in this dataset. Furthermore, the low significance of ubiquitously expressed genes involved in protein turnover ([UBC](/details-gene/7316)), RNA binding ([PABPC1](/details-gene/26986)), and iron storage ([FTH1](/details-gene/2495), [FTL](/details-gene/2512)) reinforces the highly specialized nature of this neuron's transcriptome. ## Clinical Significance and Contextual Roles While this analysis provides a general overview, the specific molecular signature of this [glutamatergic neuron](/details-cell/CL0000679) points to its potential involvement in several neurological and psychiatric disorders. The disruption of glutamatergic signaling is a central theme in many CNS pathologies. The high specificity of genes implicated in neurodevelopmental disorders is particularly noteworthy. [DSCAM](/details-gene/1826) is located on chromosome 21 and its overexpression is thought to contribute to the neurological defects observed in Down syndrome ([Link](https://doi.org/10.1093/hmg/7.2.227)). [CSMD3](/details-gene/114788) has been identified as a candidate gene for benign adult familial myoclonic epilepsy ([Link](https://doi.org/10.1016/s0006-291x(03)01555-9)), highlighting the importance of precise synaptic organization for maintaining network stability. Furthermore, the relaxin-3/[RXFP3](/details-gene/51289) signaling system, a defining feature of these cells, has been increasingly linked to the regulation of stress, anxiety, memory, and feeding behavior. Dysfunction in this pathway could contribute to the pathophysiology of mood disorders and metabolic diseases. The unexpected top marker [LGALS14](/details-gene/56891), with its known role in mediating T-cell apoptosis ([Link](https://doi.org/10.1073/pnas.0903568106)), suggests a potential role for this neuron in processes at the intersection of neuroscience and immunology, such as neuroinflammation or microglia-mediated synaptic pruning, which are increasingly recognized as factors in neurodegenerative and psychiatric conditions. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The highly specific co-expression of a diverse array of cell adhesion molecules, including the [CSMD](/details-gene/64478), [PCDH](/details-gene/56134), and [DSCAM](/details-gene/1826) families, endows this specific [glutamatergic neuron](/details-cell/CL0000679) subtype with a unique "synaptic address code" that dictates its precise connectivity and integration into a distinct functional microcircuit. * **Surprising Findings:** It is unusual for a single neuronal subtype to rely on so many different families of adhesion molecules as defining specific markers. This suggests a multi-layered system for ensuring wiring specificity that is far more complex than previously appreciated for this cell type. * **Testable Questions:** Does conditional knockout of [CSMD3](/details-gene/114788) or [DSCAM](/details-gene/1826) in this neuronal population lead to aberrant dendritic arborization, incorrect synaptic partner selection, and measurable deficits in behaviors associated with the brain region where these neurons reside? 2. **Hypothesis:** [LGALS14](/details-gene/56891), a galectin known for its immune-regulatory function in the placenta, is repurposed in this neuronal subtype to mediate neuro-immune interactions, potentially by modulating microglial activity, influencing synaptic pruning, or protecting the neuron from immune-mediated damage in the context of neuroinflammation. * **Surprising Findings:** The identification of a gene primarily characterized as "placenta-specific" ([Link](https://doi.org/10.1016/s0167-4781(01)00319-0)) as the top specificity marker for a neuronal population is a highly unexpected discovery, implying a novel and unexplored function for this protein in the central nervous system. * **Testable Questions:** Is [LGALS14](/details-gene/56891) secreted from these neurons, and does it bind to specific glycan receptors on nearby microglia or astrocytes? Does its ablation in animal models exacerbate or ameliorate neuronal damage and cognitive deficits following an inflammatory challenge like lipopolysaccharide (LPS) injection?