Details for: CL4030028

Cell ID: CL4030028

Cell Name: glycinergic amacrine cell

Description: An amacrine cell that uses glycine as a neurotransmitter.

Synonyms: amacrine cell, glycinergic

Selected Context(s): Overall

Gene Significance Landscape

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Genes

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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 glycinergic amacrine cell 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 glycinergic amacrine cell. 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 glycinergic amacrine cell. 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 glycinergic amacrine cell. 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:  glycinergic amacrine cell (CL4030028)

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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 The [glycinergic amacrine cell](/details-cell/CL4030028) is an inhibitory interneuron of the retina that utilizes glycine as its primary neurotransmitter. Based on its gene significance profile, this cell's identity is profoundly defined by a suite of genes essential for nervous system development, synaptic organization, and the reception of diverse neurotransmitter signals. The high specificity scores (**Overall**) for genes like [MDGA2](/details-gene/161357) (CSI: 38.39) and [GRIA4](/details-gene/2893) (CSI: 31.05) suggest that this cell type plays a critical role in establishing the precise wiring and functional architecture of retinal microcircuits. Its molecular signature points to a function that extends beyond simple glycinergic inhibition, encompassing the complex integration of both excitatory and inhibitory inputs to modulate visual signal processing. ## Key Characteristics and Function The molecular profile of the [glycinergic amacrine cell](/details-cell/CL4030028) is dominated by genes involved in three primary functional clusters: synaptic transmission and excitability, neural development and cell adhesion, and intracellular signaling. * **Synaptic Transmission and Signal Integration:** A defining characteristic of this cell is its expression of a wide array of neurotransmitter receptors. Despite being glycinergic, its top markers include the AMPA glutamate receptor subunit [GRIA4](/details-gene/2893) and the metabotropic glutamate receptor [GRM5](/details-gene/2915), indicating it receives significant excitatory input. Concurrently, it expresses high levels of GABA-A receptor subunits, including [GABRB2](/details-gene/2561) and [GABRG3](/details-gene/2567), suggesting it also integrates inhibitory signals from other GABAergic neurons. This complex receptor profile implies a sophisticated role in balancing excitatory and inhibitory tones within the retina. The cell's intrinsic excitability appears to be shaped by ion channels such as the hyperpolarization-activated channel [HCN1](/details-gene/348980) and the potassium channel modulating protein [KCNIP4](/details-gene/80333). * **Neural Development and Circuit Assembly:** A large number of the most specific markers are cell adhesion molecules crucial for neuronal migration, axon guidance, and synapse specification. These include [MDGA2](/details-gene/161357), [KIRREL3](/details-gene/84623), [DSCAM](/details-gene/1826), [CNTN1](/details-gene/1272), and [OPCML](/details-gene/4978). The high significance of the transcription factor [MYT1L](/details-gene/23040), a regulator of neuronal differentiation, and [NRG3](/details-gene/10718), a ligand for ErbB4 receptor tyrosine kinases, further underscores the cell's involvement in establishing and maintaining the laminated structure of the retina. The expression of [RTN4](/details-gene/57142) (Nogo), an inhibitor of neurite outgrowth, suggests this cell may also contribute to refining neural circuits by defining boundaries and preventing aberrant connections. * **Intracellular Signaling Pathways:** Key signaling molecules such as the kinase [PAK5](/details-gene/57144) and the adhesion G protein-coupled receptor [ADGRB3](/details-gene/577) are highly specific to this cell type. These proteins likely translate extracellular cues from the complex retinal environment into downstream changes in cell morphology and synaptic function. * **Anti-Markers Profile:** The least significant genes for this cell type are predominantly housekeeping genes involved in ubiquitous cellular processes, such as metabolism ([GAPDH](/details-gene/2597)), iron storage ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)), and core mitochondrial function (e.g., [COX1](/details-gene/4512), [ND1](/details-gene/4535)). The negative CSI values for these genes are characteristic of a terminally differentiated, highly specialized cell whose transcriptional program is overwhelmingly dedicated to its specific neuronal functions rather than to general metabolic or proliferative activities. ## Clinical Significance and Contextual Roles **Overall**, the gene signature of the [glycinergic amacrine cell](/details-cell/CL4030028) highlights its potential importance in neurodevelopmental and retinal disorders. The strong expression of [DSCAM](/details-gene/1826), a gene located on chromosome 21, suggests that altered function or dosage of this cell adhesion molecule in [glycinergic amacrine cells](/details-cell/CL4030028) could contribute to the neurological and visual deficits observed in Down syndrome ([Link](https://doi.org/10.1093/hmg/7.2.227)). Furthermore, the array of highly specific genes related to glutamate and GABA signaling ([GRIA4](/details-gene/2893), [GRM5](/details-gene/2915), [GABRB2](/details-gene/2561)) points to a central role in maintaining the delicate excitatory/inhibitory balance in the retina. Dysregulation of this balance is a hallmark of various retinopathies and neurological conditions, including epilepsy. The prominent expression of the transcription factor [MYT1L](/details-gene/23040) is also clinically relevant, as mutations in this gene are associated with intellectual disability and neurodevelopmental disorders. Therefore, dysfunction in [glycinergic amacrine cells](/details-cell/CL4030028) resulting from mutations in these key genes could disrupt retinal processing and potentially contribute to the pathophysiology of these broader conditions. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The [glycinergic amacrine cell](/details-cell/CL4030028) functions as a critical computational hub in the retina, integrating diverse excitatory (glutamatergic) and inhibitory (GABAergic) inputs to precisely shape the temporal and spatial output of retinal ganglion cells. * **Surprising Findings:** The striking co-expression of highly specific markers for both glutamate ([GRIA4](/details-gene/2893), [GRM5](/details-gene/2915)) and GABA ([GABRB2](/details-gene/2561), [GABRG3](/details-gene/2567)) receptors in a cell defined by its *glycinergic* output is a significant finding. This suggests its functional role is far more complex than that of a simple inhibitory relay, pointing instead to a sophisticated role in signal processing and integration. * **Testable Questions:** Can in-situ patch-clamp recordings from [glycinergic amacrine cells](/details-cell/CL4030028) (identified using a marker like [MDGA2](/details-gene/161357)) in retinal slices demonstrate distinct postsynaptic currents in response to the application of glutamate and GABA agonists? Furthermore, how does the pharmacological blockade of these receptors on amacrine cells alter the light-evoked firing patterns of downstream retinal ganglion cells? 2. **Hypothesis:** Beyond its signaling role, the [glycinergic amacrine cell](/details-cell/CL4030028) plays a fundamental architectural role during retinal development, using its unique repertoire of cell adhesion molecules to guide the stratification of neurites within the inner plexiform layer, thereby ensuring the formation of correct synaptic circuits. * **Surprising Findings:** The high specificity of [RTN4](/details-gene/57142) (Nogo), a well-known inhibitor of neurite outgrowth, is unexpected. This suggests that these cells not only form specific connections but also actively sculpt the local environment by creating "no-go" zones, a mechanism that may be essential for preventing incorrect synaptic pairings and maintaining the precise laminar organization of the retina. * **Testable Questions:** Does the conditional knockout of key adhesion genes, such as [DSCAM](/details-gene/1826) or [CNTN1](/details-gene/1272), specifically within the [glycinergic amacrine cell](/details-cell/CL4030028) population during development lead to observable defects in the lamination of the inner plexiform layer or mis-targeting of synapses from connected bipolar or retinal ganglion cells?