Details for: CL0000561

Cell ID: CL0000561

Cell Name: amacrine cell

Description: Interneuron of the vertebrate retina. They integrate, modulate, and interpose a temporal domain in the visual message presented to the retinal ganglion cells, with which they synapse in the inner plexiform layer. They lack large axons.

Synonyms: amacrine neuron, AC, ACs

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 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 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 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 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:  amacrine cell (CL0000561)

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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 [amacrine cell](/details-cell/CL0000561) is a specialized interneuron within the vertebrate retina, primarily functioning to integrate and modulate visual signals before they reach retinal ganglion cells. As revealed by its gene significance profile, this cell type is characterized by the unique expression of genes involved in complex neural circuit formation, synaptic transmission, and the active maintenance of neuronal architecture. The high specificity score for [RTN4](/details-gene/57142), an inhibitor of neurite outgrowth, alongside numerous cell adhesion and neurotransmitter receptor genes such as [NRG3](/details-gene/10718) and [GRIA4](/details-gene/2893), suggests that the core identity of the [amacrine cell](/details-cell/CL0000561) is defined by its role in sculpting, stabilizing, and fine-tuning the intricate synaptic layers of the retina. ## Key Characteristics and Function Analysis of top marker genes in the **Overall** context delineates several core functional axes for the [amacrine cell](/details-cell/CL0000561). * **Synaptic Signaling and Neurotransmission:** A prominent feature of the [amacrine cell](/details-cell/CL0000561) is its extensive machinery for neurotransmission. The high significance of genes encoding subunits for both excitatory and inhibitory receptors, such as the AMPA glutamate receptor subunit [GRIA4](/details-gene/2893) and GABA-A receptor subunits [GABRG3](/details-gene/2567) and [GABRB1](/details-gene/2560), underscores its central role as an integrator of diverse inputs. This is further supported by the expression of [KCND2](/details-gene/3751), a voltage-gated potassium channel essential for shaping action potentials, and [SLC24A2](/details-gene/25769), a potassium-dependent sodium-calcium exchanger critical for ionic homeostasis in retinal neurons ([Link](https://doi.org/10.1523/jneurosci.20-04-01424.2000)). The expression of [SYNPR](/details-gene/132204), a synaptic vesicle protein, points to its active role in neurotransmitter release. * **Neuronal Architecture and Circuit Maintenance:** The [amacrine cell's](/details-cell/CL0000561) identity is profoundly linked to establishing and maintaining precise retinal circuitry. The top marker, [RTN4](/details-gene/57142), is a well-known inhibitor of neurite outgrowth, suggesting a critical function in restricting neuronal processes to specific laminae within the inner plexiform layer, thus ensuring circuit fidelity. This is complemented by a suite of cell adhesion molecules, including [DSCAM](/details-gene/1826), which is vital for neuronal wiring and self-avoidance ([Link](https://doi.org/10.1093/hmg/7.2.227)), [OPCML](/details-cell/CL0000561), [KIRREL3](/details-gene/84623), and [CNTNAP5](/details-gene/129684). Furthermore, the specific expression of [NRG3](/details-gene/10718), a ligand for the ErbB4 receptor, highlights a role for neuregulin signaling in retinal development and function, potentially modulating synaptogenesis and cell survival ([Link](https://doi.org/10.1073/pnas.94.18.9562)). * **Transcriptional and Post-Transcriptional Regulation:** A complex network of regulatory genes maintains the unique state of the [amacrine cell](/details-cell/CL0000561). Key markers include the transcription factor [MYT1L](/details-gene/23040), the transcription elongation factor component [ELOB](/details-gene/6923), and the long non-coding RNA [NEAT1](/details-gene/283131), a core component of nuclear paraspeckles involved in gene regulation. The expression of RNA-binding proteins like [DDX17](/details-gene/10521) and [PNISR](/details-gene/25957) further indicates that sophisticated control of RNA processing and splicing is essential for this cell's function. * **Cellular Identity Profile:** The anti-marker profile helps define what this cell is not. The strong negative significance score for [B2M](/details-gene/567), a core component of MHC Class I molecules, is consistent with the immune-privileged status of many central nervous system neurons, suggesting low antigen presentation capacity. The relatively low significance of multiple mitochondrially-encoded genes (e.g., [COX1](/details-gene/4512), [COX3](/details-gene/4514), [CYTB](/details-gene/4519), [ND1](/details-gene/4535)) does not imply a lack of mitochondria, but rather that their expression is not a defining feature compared to other, potentially more metabolically demanding, retinal cells like photoreceptors. ## Clinical Significance and Contextual Roles The unique molecular profile of the [amacrine cell](/details-cell/CL0000561) implicates it in several neurodevelopmental and neurological disorders. The high significance of [DSCAM](/details-gene/1826), the Down syndrome cell adhesion molecule, strongly suggests that dysfunction of [amacrine cells](/details-cell/CL0000561) may contribute to the visual and neurological phenotypes observed in Down syndrome. Altered [DSCAM](/details-gene/1826) dosage could disrupt the precise lamination and synaptic connectivity within the retina, leading to impaired visual processing ([Link](https://doi.org/10.1093/hmg/7.2.227)). Furthermore, several top markers are linked to broader neurological conditions. [NRG3](/details-gene/10718) and its receptor have been implicated as risk factors for schizophrenia, suggesting that aberrant signaling in retinal circuits involving [amacrine cells](/details-cell/CL0000561) could mirror or contribute to central nervous system pathologies. The gene [CSMD3](/details-gene/114788) is a candidate for benign adult familial myoclonic epilepsy ([Link](https://doi.org/10.1016/s0006-291x(03)01555-9)), while mutations in the transcription factor [MYT1L](/details-gene/23040) are associated with a syndrome of intellectual disability. These associations highlight the [amacrine cell](/details-cell/CL0000561) as a potential site where genetic risk factors for diverse neurological disorders may manifest, impacting retinal function and potentially serving as a window into brain-wide disease processes. ## Potential Mechanisms and Research Directions 1. **Hypothesis: [RTN4](/details-gene/57142) as a "Molecular Fence" for Retinal Circuit Integrity.** The highly specific expression of the potent neurite outgrowth inhibitor [RTN4](/details-gene/57142) in mature [amacrine cells](/details-cell/CL0000561) suggests it functions as a dynamic structural stabilizer. We hypothesize that [RTN4](/details-gene/57142) actively maintains the precise stratification of amacrine cell dendrites within the inner plexiform layer by acting as a "molecular fence," preventing aberrant sprouting into incorrect sublaminae and thereby preserving the functional integrity of specialized visual channels (e.g., ON vs. OFF pathways). * **Surprising Findings:** It is unexpected for a mature, stable neuron to feature a potent growth inhibitor as its top defining marker. This challenges the view of neuronal structure as static, suggesting instead that it requires continuous, active enforcement of boundaries. * **Testable Questions:** Does conditional knockout of [RTN4](/details-gene/57142) specifically in adult mouse [amacrine cells](/details-cell/CL0000561) lead to age-dependent de-stratification of their dendritic arbors and a corresponding decline in direction-selective or other complex visual responses measured by electroretinography or two-photon calcium imaging? 2. **Hypothesis: [NRG3](/details-gene/10718) as a Modulator of Synaptic Plasticity.** The co-expression of the neuregulin [NRG3](/details-gene/10718) alongside a full complement of classical neurotransmitter receptors ([GRIA4](/details-gene/2893), [GABRG3](/details-gene/2567)) points to a dual-layered signaling system. We hypothesize that [NRG3](/details-gene/10718) acts as a paracrine signal that modulates the gain and plasticity of conventional glutamatergic and GABAergic synapses on [amacrine cells](/details-cell/CL0000561) and their post-synaptic partners. This pathway may mediate slower, adaptive changes in retinal circuitry in response to prolonged changes in visual input or developmental state. * **Surprising Findings:** The prominence of a growth factor-like signaling pathway ([NRG3](/details-gene/10718)-ErbB4) in a cell defined by fast synaptic transmission suggests a layer of "meta-plasticity" that governs how these rapid circuits adapt over time. The identification of NRG3 as a neural-enriched ligand for ErbB4 supports this specialized role ([Link](https://doi.org/10.1073/pnas.94.18.9562)). * **Testable Questions:** Using patch-clamp electrophysiology in retinal slices, does acute application of recombinant [NRG3](/details-gene/10718) alter the amplitude or kinetics of AMPA- or GABA-mediated postsynaptic currents in [amacrine cells](/details-cell/CL0000561)? Does genetic deletion of [NRG3](/details-gene/10718) or its receptor ErbB4 in the retina impair processes like light adaptation or contrast sensitivity?