Biology subjects

Jaroszynska, N.

Publications and source records attributed to Jaroszynska, N..

3 recordsLinked to original sources

bioRxiv2025

Gelatinase activity is required for Muller glia morphogenesis and neuronal maintenance in the retina

Glial cells are indispensable support elements of the nervous system, yet the mechanisms by which they integrate into densely packed, extracellular matrix (ECM)-rich cellular environments remain poorly understood. In the retina, Muller glia (MG) serve as the principal support cells, performing roles analogous to astrocytes in the brain. As late-born retinal cells, MG undergo morphogenesis within a complex extracellular milieu composed of neighbouring neurons, synapses, and ECM components. Using the zebrafish retina, we show that developing MG dynamically interact with the ECM across all retinal layers while expressing the ECM-remodelling enzymes matrix metalloproteinases (Mmp) 2 and 9. Although Mmps are known to contribute to tissue remodelling and disease processes such as glioma invasion, their developmental roles in glia remain less defined. Here, we demonstrate that Mmp2 and Mmp9 are required for MG morphogenesis and glia-neuron integration. Pharmacological inhibition or genetic loss of mmp2 and mmp9 impaired MG outgrowth and reduced process complexity within synaptic layers, leading to decreased MG-synapse associations. Double mutants (mmp2-/-;mmp9-/-) displayed normal neuronal development and visual function at larval stages but exhibited gliosis, premature neurodegeneration, and visual deficits in adulthood. Together, these findings reveal that Mmp2 and Mmp9 are critical for establishing MG-synapse interactions during development and for maintaining neuronal integrity and visual function in the mature retina.

neuroscience↗

bioRxiv2023

Alternative splicing controls teneurin-3 compact dimer formation for neuronalrecognition

Neuronal network formation is facilitated by recognition between synaptic cell adhesion molecules (CAMs) at the cell surface. Alternative splicing of CAMs provides additional specificity in forming neuronal connections. For the teneurin family of CAMs, alternative splicing of the EGF-repeats and NHL domain controls protein-protein interactions at the synapse. Here we present a 3.2 [A] cryo-EM structure of the compact dimeric ectodomain of teneurin-3 harbouring both splice inserts. This dimer is stabilised by an EGF8-ABD contact between subunits. Cryo-EM reconstructions of all four splice variants, together with SAXS and negative stain EM, reveal compacted dimers for each, with variant-specific dimeric arrangements. This results in specific trans-cellular interactions, as tested in cell clustering and stripe assays. The compact conformations provide a structural basis for teneurin homo- and heterophilic interactions. Altogether, our findings demonstrate how alternative splicing results in rearrangements of the dimeric subunits, influencing neuronal recognition and circuit wiring.

biochemistry↗

bioRxiv2023

C9ORF72 deficiency results in degeneration of the zebrafish retina in vivo

G4C2 Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting haploinsufficiency could contribute to disease. To further understand the consequences of C9ORF72 deficiency in vivo, we generated a c9orf72 mutant zebrafish line. Analysis of the spinal cord revealed no appreciable neurodegenerative pathology such as loss of motor neurons, or increased levels of neuroinflammation. However, detailed examination of c9orf72-/- retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Structurally, analysis of rod and cone cells within the photoreceptor layer showed a disturbance in the outer cells of the retina and rhodopsin mis-localisation from rod outer segments to their cell bodies and synaptic endings. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss.

neuroscience↗