Biology subjects

Kucenas, S.

Publications and source records attributed to Kucenas, S..

6 recordsLinked to original sources

bioRxiv2026

Tenascin N contributes to spinal motor nerve morphogenesis during development

Spinal motor nerves are an integral component of the nervous system whose development requires the coordination of many diverse cell types, including motor neurons, glia, and muscle. Although several molecular mechanisms guiding these interactions are known, many remain to be uncovered. Extracellular matrix (ECM) proteins also play a critical role in motor nerve assembly, yet their functions are less understood compared to classical pathfinding and guidance cues. Here, we identify a role for tenascin-n (tnn), an ECM glycoprotein, in spinal motor nerve development in zebrafish. Using in situ hybridization and immunohistochemistry, we show that tnn/Tnn is expressed and localized along vertical myosepta and the border of the ventral neural tube during spinal motor nerve development. To assess its function, we generated a CRISPR/Cas9 mutant allele, tnnuva96, and performed in vivo imaging and morphological analysis throughout motor nerve development. Loss of tnn leads to a subtle and transient increase in ectopic motor axon exit and aberrant motor axon branching in the zebrafish trunk. Our findings reveal a previously unrecognized role for tnn in spinal motor nerve assembly and expand our understanding of the diverse molecular contributors to spinal motor nerve development and morphogenesis.

developmental biology↗

bioRxiv2025

Radial astroglia cooperate with microglia to clear neuronal cell bodies during zebrafish optic tectum development

The clearance of dead cells by phagocytes is an essential component of neural development in many organisms. Microglia are the main phagocytes in the central nervous system (CNS), but the extent of participation by other glial cells remains unclear, especially under homeostatic conditions. During zebrafish optic tectum (OT) development, we observed radial astroglia forming dynamic, spherical projections from their basal processes. These projections, which we call scyllate heads, coincide with a wave of neuronal cell death in the OT. We show that scyllate heads surround the majority of dying neurons soon after phosphatidylserine exposure. However, unlike traditional phagosomes, scyllate heads persist for many hours and are rarely acidified or internalized. Instead, microglia invade scyllate heads and remove their contents for terminal degradation. Our study reveals an active role for radial astroglia in homeostatic cell clearance and cooperation between microglia and radial astroglia during zebrafish OT development. HighlightsO_LIOptic tectum astroglia form large, dynamic projections called scyllate heads C_LIO_LIScyllate heads surround the majority of dying neurons during a wave of apoptosis C_LIO_LIScyllate heads are intermediate containers of dying cells rather than phagosomes C_LIO_LIMicroglia invade scyllate heads to remove their contents for terminal degradation C_LI

neuroscience↗

bioRxiv2024

Axonal spheroids are regulated by Schwann cells after peripheral nerve injury

Axonal spheroids are hallmark features of neurodegeneration, forming along degenerating axons and contributing to disease progression. Despite their ubiquity across degenerative etiologies, the dynamics of spheroid disappearance, as well as their interactions with glial cells, remain poorly understood. Here, using an in vivo zebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells. These results describe spheroid dynamics across their lifetimes, establish a role for the extra-axonal environment in altering spheroid outcomes, and identify a cellular mechanism whereby spheroid fates are altered. SummaryO_LIAxonal spheroids (also called "dystrophic neurites," "axonal swellings," and "axonal beading") undergo three fates: shrinking, breakdown, and uniform disappearance C_LIO_LISchwann cells ensheath most axonal spheroids and internalize a subset of them C_LIO_LISchwann cells regulate axonal spheroid fates, identifying a role for axon-extrinsic processes in spheroid regulation C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/622649v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@16084eeorg.highwire.dtl.DTLVardef@1b72b17org.highwire.dtl.DTLVardef@6e2b47org.highwire.dtl.DTLVardef@db4ccb_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Following injury, spheroids are more likely to undergo shrinking and breakdown when Schwann cells (SCs) are present on degenerating axons. When Schwann cells are absent, spheroids are more likely to undergo uniform disappearance. Spheroids expose phosphatidylserine, which could facilitate interactions between spheroids and SCs. C_FIG

neuroscience↗

bioRxiv2022

Cd59 and inflammation orchestrate Schwann cell development

Efficient neurotransmission is essential for organism survival and is enhanced by myelination. However, the genes that regulate myelin and myelinating glial cell development have not been fully characterized. Data from our lab and others demonstrates that cd59, which encodes for a small GPI-anchored glycoprotein, is highly expressed in developing zebrafish, rodent, and human oligodendrocytes (OLs) and Schwann cells (SCs), and that patients with CD59 dysfunction develop neurological dysfunction during early childhood. Yet, the function of CD59 in the developing nervous system is currently undefined. In this study, we demonstrate that cd59 is expressed in a subset of developing SCs. Using cd59 mutant zebrafish, we show that developing SCs proliferate excessively, which leads to reduced myelin volume, altered myelin ultrastructure, and perturbed node of Ranvier assembly. Finally, we demonstrate that complement activity is elevated in cd59 mutants and that inhibiting inflammation restores SC proliferation, myelin volume, and nodes of Ranvier to wildtype levels. Together, this work identifies Cd59 and developmental inflammation as key players in myelinating glial cell development, highlighting the collaboration between glia and the innate immune system to ensure normal neural development.

neuroscience↗

bioRxiv2021

Met is required for oligodendrocyte progenitor cell migration in Danio rerio

During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.

neuroscience↗

bioRxiv2020

Spinal cord precursors utilize neural crest cell mechanisms to generate hybrid peripheral myelinating glia

During development, oligodendrocytes and Schwann cells myelinate central and peripheral nervous system axons, respectively, while motor exit point (MEP) glia are neural tube-derived, peripheral glia that myelinate axonal territory between these populations at MEP transition zones. From which specific neural tube precursors MEP glia are specified, and how they exit the neural tube to migrate onto peripheral motor axons, remain largely unknown. Here, using zebrafish, we found that MEP glia arise from lateral floor plate precursors and require foxd3 to delaminate and exit the spinal cord. Additionally, we show that similar to Schwann cells, MEP glial development depends on axonally-derived neuregulin1. Finally, our data demonstrate that overexpressing axonal cues is sufficient to generate additional MEP glia in the spinal cord. Overall, these studies provide new insight into how a novel population of hybrid, peripheral myelinating glia are generated from neural tube precursors and migrate into the periphery.

developmental biology↗