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 zebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells.

Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord.

The central and peripheral nervous systems (CNS and PNS, respectively) exhibit remarkable diversity in the capacity to regenerate following neuronal injury with PNS injuries being much more likely to regenerate than those that occur in the CNS. Glial responses to damage greatly influence the likelihood of regeneration by either promoting or inhibiting axonal regrowth over time. However, despite our understanding of how some glial lineages participate in nerve degeneration and regeneration, less is known about the contributions of peripheral satellite glial cells (SGC) to regeneration failure following central axon branch injury of dorsal root ganglia (DRG) sensory neurons.

Rohon-beard neurons do not succumb to programmed cell death during zebrafish development.

During neural development, sculpting of early formed circuits by cell death and synaptic pruning is necessary to generate a functional and efficient nervous system. This allows for the establishment of rudimentary circuits which necessitate early organism survival to later undergo subsequent refinement. These changes facilitate additional specificity to stimuli which can lead to increased behavioral complexity.

Glia at Transition Zones.

Neural cells are segregated into their distinct central nervous system (CNS) and peripheral nervous system (PNS) domains. However, at specialized regions of the nervous system known as transition zones (TZs), glial cells from both the CNS and PNS are uniquely present with other specialized TZ cells. Herein we review the current understanding of vertebrate TZ cells.

Chimeric efferocytic receptors improve apoptotic cell clearance and alleviate inflammation.

Our bodies turn over billions of cells daily via apoptosis and are in turn cleared by phagocytes via the process of "efferocytosis." Defects in efferocytosis are now linked to various inflammatory diseases. Here, we designed a strategy to boost efferocytosis, denoted "chimeric receptor for efferocytosis" (CHEF).

Cd59 and inflammation regulate 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 , 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.

Transforming growth factor-beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish.

Spinal motor nerves are necessary for organismal locomotion and survival. In zebrafish and most vertebrates, these peripheral nervous system structures are composed of bundles of axons that naturally regenerate following injury. However, the cellular and molecular mechanisms that mediate this process are still only partially understood.

Clearing Your Mind: Mechanisms of Debris Clearance After Cell Death During Neural Development.

Neurodevelopment and efferocytosis have fascinated scientists for decades. How an organism builds a nervous system that is precisely tuned for efficient behaviors and survival and how it simultaneously manages constant somatic cell turnover are complex questions that have resulted in distinct fields of study. Although neurodevelopment requires the overproduction of cells that are subsequently pruned back, very few studies marry these fields to elucidate the cellular and molecular mechanisms that drive nervous system development through the lens of cell clearance.

zMADM (zebrafish mosaic analysis with double markers) for single-cell gene knockout and dual-lineage tracing.

As a vertebrate model organism, zebrafish has many unique advantages in developmental studies, regenerative biology, and disease modeling. However, tissue-specific gene knockout in zebrafish is challenging due to technical difficulties in making floxed alleles. Even when successful, tissue-level knockout can affect too many cells, making it difficult to distinguish cell autonomous from noncell autonomous gene function.

Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System.

Tiling is a developmental process where cell populations become evenly distributed throughout a tissue. In this review, we discuss the developmental cellular tiling behaviors of the two major glial populations in the central nervous system (CNS)-oligodendrocyte progenitor cells (OPCs) and astrocytes. First, we discuss OPC tiling in the spinal cord, which is comprised of the three cellular behaviors of migration, proliferation, and contact-mediated repulsion (CMR).

A novel gene trap line for visualization and manipulation of erbb3b neural crest and glial cells in zebrafish.

Glia are a diverse and essential cell type in the vertebrate nervous system. Transgenic tools and fluorescent reporter lines are critical resources to investigate how glial subtypes develop and function. However, despite the many lines available in zebrafish, the community still lacks the ability to label all unique stages of glial development and specific subpopulations of cells.

Diversity and convergence within peripheral glia development.

In a recent study, Tasdemir-Yilmaz and colleagues used single-cell RNA sequencing to reveal how diversity among peripheral glia changes with development and also identified unifying genetic profiles that are shared between mature glia. These data highlight new tools and pathways in which to understand peripheral glial development and function.

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.

A Novel Lysolecithin Model for Visualizing Damage in the Larval Zebrafish Spinal Cord.

Lysolecithin is commonly used to induce demyelinating lesions in the spinal cord and corpus callosum of mammalian models. Although these models and clinical patient samples are used to study neurodegenerative diseases, such as multiple sclerosis (MS), they do not allow for direct visualization of disease-related damage . To overcome this limitation, we created and characterized a focal lysolecithin injection model in zebrafish that allows us to investigate the temporal dynamics underlying lysolecithin-induced damage .

Glutamate Signaling via the AMPAR Subunit GluR4 Regulates Oligodendrocyte Progenitor Cell Migration in the Developing Spinal Cord.

Oligodendrocyte progenitor cells (OPCs) are specified from discrete precursor populations during gliogenesis and migrate extensively from their origins, ultimately distributing throughout the brain and spinal cord during early development. Subsequently, a subset of OPCs differentiates into mature oligodendrocytes, which myelinate axons. This process is necessary for efficient neuronal signaling and organism survival.

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 to delaminate and exit the spinal cord.

Engulfed by Glia: Glial Pruning in Development, Function, and Injury across Species.

Phagocytic activity of glial cells is essential for proper nervous system sculpting, maintenance of circuitry, and long-term brain health. Glial engulfment of apoptotic cells and superfluous connections ensures that neuronal connections are appropriately refined, while clearance of damaged projections and neurotoxic proteins in the mature brain protects against inflammatory insults. Comparative work across species and cell types in recent years highlights the striking conservation of pathways that govern glial engulfment.

How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World.

The COVID19 crisis has magnified the issues plaguing academic science, but it has also provided the scientific establishment with an unprecedented opportunity to reset. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers.

Migratory Neural Crest Cells Phagocytose Dead Cells in the Developing Nervous System.

During neural tube closure and spinal cord development, many cells die in both the central and peripheral nervous systems (CNS and PNS, respectively). However, myeloid-derived professional phagocytes have not yet colonized the trunk region during early neurogenesis. How apoptotic cells are removed from this region during these stages remains largely unknown.

The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones.

During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood.

DETECTION AND TRACKING OF MIGRATING OLIGODENDROCYTE PROGENITOR CELLS FROM FLUORESCENCE TIME-LAPSE IMAGING DATA.

In this work, we develop a fully automatic algorithm named "MCDT" (Migrating Cell Detector and Tracker) for the integrated task of migrating cell detection, segmentation and tracking from fluorescence time-lapse microscopy imaging data. The interest of detecting and tracking migrating cells arouses from the scientific question in understanding the impact of oligodendrocyte progenitor cells (OPCs) migration , using advanced microscopy imaging techniques. Current practice of OPC mobility analysis relies on manual labeling, suffering from massive human labor, subjective biases, and weak reproducibility.

Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release.

Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional phagocytes via efferocytosis. How a phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood.

Motor Exit Point (MEP) Glia: Novel Myelinating Glia That Bridge CNS and PNS Myelin.

Oligodendrocytes (OLs) and Schwann cells (SCs) have traditionally been thought of as the exclusive myelinating glial cells of the central and peripheral nervous systems (CNS and PNS), respectively, for a little over a century. However, recent studies demonstrate the existence of a novel, centrally-derived peripheral glial population called motor exit point (MEP) glia, which myelinate spinal motor root axons in the periphery. Until recently, the boundaries that exist between the CNS and PNS, and the cells permitted to cross them, were mostly described based on fixed histological collections and static lineage tracing.

Purinergic signaling in oligodendrocyte development and function.

Myelin, an insulating membrane that enables rapid action potential propagation, is an essential component of an efficient, functional vertebrate nervous system. Oligodendrocytes, the myelinating glia of the central nervous system (CNS), produce myelin throughout the CNS, which requires continuous proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Because myelination is essential for efficient neurotransmission, researchers hypothesize that neuronal signals may regulate the cascade of events necessary for this process.

Livin' On The Edge: glia shape nervous system transition zones.

The vertebrate nervous system is divided into two functional halves; the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which consists of nerves and ganglia. Incoming peripheral stimuli transmitted from the periphery to the CNS and subsequent motor responses created because of this information, require efficient communication between the two halves that make up this organ system. Neurons and glial cells of each half of the nervous system, which are the main actors in this communication, segregate across nervous system transition zones and never mix, allowing for efficient neurotransmission.