Biology subjects

Jalufka, F. L.

Publications and source records attributed to Jalufka, F. L..

4 recordsLinked to original sources

bioRxiv2025

Functional synaptic connectivity of engrafted spinal cord neurons with locomotor circuitry in the injured spinal cord

Spinal cord injury (SCI) results in significant neurological deficits, with no currently available curative therapies. Neural progenitor cell (NPC) transplantation has emerged as a promising approach for neural repair, as graft-derived neurons (GDNs) can integrate into the host spinal cord and support axon regeneration. However, the mechanisms underlying functional recovery remain poorly understood. In this study, we investigate the synaptic integration of NPC-derived neurons into locomotor circuits, the projection patterns of distinct neuronal subtypes, and their potential to modulate motor circuit activity. Using transsynaptic tracing in a mouse thoracic contusion SCI model, we found that NPC-derived neurons form synaptic connections with host locomotor circuits, albeit at low frequencies. Furthermore, we mapped the axon projections of V0C and V2a interneurons, revealing distinct termination patterns within host spinal cord laminae. To assess functional integration, we employed chemogenetic activation of GDNs, which induced muscle activity in a subset of transplanted animals. However, NPC transplantation alone did not significantly improve locomotor recovery, highlighting a key challenge in the field. Our findings suggest that while GDNs can integrate into host circuits and modulate motor activity, synaptic connectivity remains a limiting factor in functional recovery. Future studies should focus on enhancing graft-host connectivity and optimizing transplantation strategies to maximize therapeutic benefits for SCI.

neuroscience↗

bioRxiv2025

Rapid and efficient optical tissue clearing for volumetric imaging of the intact and injured spinal cord in mice

Tissue clearing and 3D imaging have emerged as powerful techniques to assess the cellular and tissue-level architecture of the spinal cord. With the rapidly increasing variety and complexity of optical tissue clearing techniques, there is a critical need for optimization and streamlining of tissue-specific protocols, particularly when dealing with injury or disease states. We evaluated and combined multiple organic solvent-based techniques to develop sciDISCO: a spinal cord injury-optimized DISCO tissue clearing protocol. sciDISCO allows for the robust clearing, labeling, and 3D imaging of the intact spinal cord, as well as clearing around and through the lesion site formed after contusive spinal cord injury. In addition, we have identified alternatives for hazardous chemicals commonly used in organic solvent-based clearing including dichloromethane and dibenzyl ether. In this study, we demonstrate the compatibility of sciDISCO with multiple different labeling techniques to provide robust analysis of unique neuronal populations and morphologies in addition to cellular and tissue-level changes occurring following spinal cord injury.

neuroscience↗

bioRxiv2021

Passive clearing and 3D lightsheet imaging of the intact and injured spinal cord in mice

The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal cord injury (SCI) permanently disrupts neural circuits through initial mechanical damage, as well as a cascade of secondary injury events that further expand the spinal cord lesion, resulting in permanent paralysis. Tissue clearing and 3D imaging have recently emerged as promising techniques to improve our understanding of the complex neural circuitry of the spinal cord and the changes that result from damage due to SCI. However, the application of this technology for studying the intact and injured spinal cord remains limited. Here we optimized the passive CLARITY technique (PACT) to obtain gentle and efficient clearing of the murine spinal cord without the need for specialized equipment. We demonstrate that PACT clearing enables 3D imaging of multiple fluorescent labels in the spinal cord to assess molecularly defined neuronal populations, acute inflammation, long-term tissue damage, and cell transplantation. Collectively, these procedures provide a framework for expanding the utility of tissue clearing to enhance the study of spinal cord neural circuits, as well as cellular- and tissue-level changes that occur following SCI.

neuroscience↗

bioRxiv2020

The complex evolution of the HSP70 gene family

The metazoan 70-kDa heat shock protein (HSP70) family contains several members localized in different subcellular compartments. The cytosolic members have been classified into inducible HSP70s and constitutive heat shock cognates (HSC70s), but their distinction and evolutionary relationship remain unclear because of occasional reports of "constitutive HSP70s" and the lack of cross-phylum comparisons. Here we provide novel insights into the evolution of these important molecular chaperones. Phylogenetic analyses of [~]100 full-length HSP70s revealed an ancient duplication that gave rise to two lineages from which all metazoan cytosolic HSP70s descend. One lineage (A) contains a relatively small number of Lophotrochozoan and Ecdysozoan genes, none of which have been shown to be constitutively expressed (i.e., either inducible or unknown). The other lineage (B) included both inducible and constitutive genes from diverse phyla. Species-specific duplications are present in both lineages, and Lineage B contains well-supported phylum-specific clades for Rotifera, Nematoda, and Chordata. Some genes in Lineage B have likely independently acquired inducibility, which may explain the sporadic distribution of "HSP70" or "HSC70" in previous analyses. Consistent with the diversification history within each group, inducible members show lower purifying selection pressure compared to constitutive members. These results illustrate the evolutionary history of the HSP70 family, encouraging us to propose a new nomenclature: "HSP70 + subcellular localization + linage + copy number in the organism + inducible or constitutive, if known." e.g., HSP70cA1i for cytosolic Lineage A, copy 1, inducible.

evolutionary biology↗