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The localization of mRNAs within axons and dendrites allows neurons to manipulate protein levels in a time and location dependent manner and is essential for processes such as synaptic plasticity and axon guidance. However, an essential step in the process of mRNA localization, the decision to traffic to dendrites and/or axons, remains poorly understood. Here we show that Myosin Va and actin filaments are necessary for the dendritic localization of the mRNA binding protein Staufen 1 and of mRNA encoding the microtubule binding protein Map2. Blocking the function or expression of Myosin Va or depolymerizing actin filaments leads to localization of Staufen 1 and of Map2 mRNA in both axons and dendrites. Furthermore, interaction with Myosin Va plays an instructive role in the dendritic localization of Hermes 1, an RNA binding protein. Wild-type Hermes 1 localizes to both axons and dendrites, whereas Hermes 1 fused with a Myosin Va binding peptide, localizes specifically to dendrites. Thus, our results suggest that targeting of mRNAs to the dendrites is mediated by a mechanism that is dependent on actin and Myosin Va.
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Proc Natl Acad Sci U S A
September 2025
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202.
Retinal ganglion cells (RGCs) are highly compartmentalized neurons whose long axons serve as the sole connection between the eye and the brain. In both injury and disease, RGC degeneration occurs in a similarly compartmentalized manner, with distinct molecular and cellular responses in the axonal and somatodendritic regions. The goal of this study was to establish a microfluidic-based platform to investigate RGC compartmentalization in both health and disease states.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Mudanjiang Collaborative Innovation Center for development and application of Northern Medicine Resources, Mudanjiang, PR China; Institute of Neural Tissue Engineering, Mudanjiang Medical University, Mudanjiang, Heilongjiang, PR China. Electronic address:
Spinal cord injury (SCI) causes irreversible motor deficits due to disrupted lumbar circuitry. However, transcriptional mechanisms in distal lumbar circuits are poorly understood. We identify POU6F1 as a critical transcriptional regulator in spinal lumbar segment (SLS, L3-L5) motor circuit regeneration.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Biology, Providence College, Providence, Rhode Island, United States of America.
In Npc1 deficient mice, postnatal developmental alterations in cerebellar microglia and Purkinje cells (PCs) are followed by early-onset neurodegeneration. Even in the absence of PC loss, microglia in Npc1nmf164 mice display hallmark features of activation during early postnatal development, including increased proliferation, enhanced phagocytic activity, and morphological changes indicative of an activated state. In this study, we investigated whether mammalian target of rapamycin complex 1 (mTORC1) drives postnatal activation of cerebellar microglia in Npc1nmf164 mice.
View Article and Find Full Text PDFJ Adv Res
September 2025
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China. Electronic address:
Introduction: Parkinson's disease (PD) is characterized by early synaptic and axonal dysfunction, driven by α-synuclein (α-Syn, encoded by the SNCA gene) aggregation. The axon guidance molecules play critical roles in neuronal integrity, yet their dysregulation in PD remains underexplored.
Objectives: This study aimed to demonstrate how α-Syn preformed fibrils (PFFs) alter the expression of axon guidance molecules, contributing to early synucleinopathy, and to evaluate the therapeutic potential of netrin-1 (NTN1).
Gels
August 2025
Department of Pure and Applied Physics, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.
Axon polarization is a fundamental process in neuronal development, providing the structural basis for directional signaling in neural circuits. Precise control of axon specification is, thus, essential for the bottom-up construction of neuronal networks with defined architecture and connectivity. Although neurite length and elongation timing have both been implicated as determinants of axonal fate, their relative contributions have remained unresolved due to technical limitations in manipulating these factors independently in conventional culture systems.
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