Description
The contact of glial cells with neurons is necessary for the development of the central nervous system. This process is facilitated by the distinctive morphologies of glial cells that allow precise spatial contact with neurons. Specifically, glial cells and neurons form functional compartments at the synapse where the glial projection ensheathes the pre- and post-synaptic terminals. Among glial cells, the Müller glia (MG) is the primary synaptic astroglia of the retina that plays multiple roles during retinal development. MG extends across the inner plexiform layer (IPL) and forms precise circuits with neurons during retinal development. The formation of such morphology is important since abnormal glial morphology is a consistent characteristic in multiple neurological disorders. However, the exact mechanisms of MG morphology establishment and precise synaptic contacts are not well studied. To further characterize these processes, genes of interest are selected from a zebrafish retinal single-cell RNA sequencing database. Hybridization chain reaction (HCR) and immunohistochemistry are then performed to assess specific expression in MG and contacted neurons, spatially validating the genes of interest. Subsequently, crispant knock-out or knock-down models are generated to assess phenotypic outcomes, thus explaining the roles of these genes in MG morphology and MG-neuron contact. This study aims to define the molecular mechanisms underlying MG morphogenesis and neuron–glial connectivity during retinal development. Clarifying these mechanisms will advance understanding of MG function in retinal development and may also give insights into the contribution of glial dysfunction to neurological diseases.
Lay Abstract
The central nervous system consists of two types of cells: neurons and glial cells. Glial cells are supporting cells that help regulate the signal-transmitting neurons. They form connections with neurons by assuming special structures that reach towards and envelop the neuron’s connection points. This process is critical since malfunctioning glial structure is commonly found in most neurological diseases. Müller glia (MG) are glial cells in the eye; their structure and precise contacts with neurons are essential for proper visual function. We study what makes MG cells branch toward and connect with neurons when the eye is young in developing zebrafish. We start by searching for candidate genes that participate in this process from a database recording when and where genes are active. The candidates are labeled with fluorescent tags, and their presence is confirmed in the interacting MG-neuron cells by looking for those tags. We then edit these genes in the fish so they don’t express at all or express less, depriving them of their function, to see if the gene is necessary for the MG structure and neuronal connections. This allows us to learn more about eye development and problems or disorders caused by dysfunctional glia as a result.
| Lay Title | Understanding How Müller Glial Cells Shape Neuron Connections and Guide Early Eye Development |
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| Role | Master Student |