Biology subjects

Min, E.

Publications and source records attributed to Min, E..

6 recordsLinked to original sources

bioRxiv2026

Nidogen/NID-1 guides regenerating motor axons in the mature nervous system

Restoring function to injured axons requires not only regeneration, but also accurate guidance and synapse reformation. Our understanding of how regenerating axons navigate the mature nervous system remains limited, as growth cones confront a cellular and molecular landscape distinct from development. Using Caenorhabditis elegans, we found that the basement membrane protein Nidogen (NID-1) promotes local guidance of regenerating motor axons in the mature nervous system by facilitating their growth alongside neighboring intact neuronal processes. Regenerating cholinergic axons preferentially track the branched dendrites of the PVD mechanosensory neuron or, in the absence of PVD dendrites, are guided alongside GABAergic commissures instead. Loss of nid-1 disrupts this guidance, reducing axon-PVD colocalization, increasing displacement from the pre-injury point of contact with the dorsal nerve cord, and disrupting synapse reformation and functional recovery. Tissue-specific rescue indicates that NID-1 expressed by body wall muscles or the hypodermis is sufficient to guide regenerating axons, whereas muscle-derived NID-1 is required to restore synapse reformation. Genetic data indicate that NID-1 function guides regenerating axons in coordination with laminin and integrin. Although this complex primarily directs cholinergic motor axons, ectopic integrin expression in GABAergic neurons is sufficient to reroute their regenerating axons alongside PVD dendrites in a NID-1-dependent manner. Together, these findings identify a NID-1-dependent post-developmental mechanism for directing regenerating axons and promoting functional repair.

neuroscience↗

bioRxiv2025

Inhibiting Clarinet/CLA-1 restores function to injured motor neurons

To regain function, injured axons need to both regenerate and reform synapses with appropriate postsynaptic cells. We found that inhibiting the scaffolding protein Clarinet/CLA-1, a C. elegans ortholog of Piccolo and Fife, robustly improves axon regeneration. Despite the importance of CLA-1 during synapse development, disrupting the medium isoform of CLA-1 increases the number of axons that regenerate to the neuromuscular junction without significantly influencing synapse reformation. Consequently, the axons that do regenerate are capable of regaining function. Mechanistically, the enhanced axon regeneration observed in cla-1(-) mutants depends on the function of PTRN-1, a microtubule minus-end binding protein. Our data supports a model where loss of CLA-1 promotes PTRN-1 function, which speeds trafficking of injury-related cargo to and from the lesion, thus improving repair. Together, our results reveal a highly conserved synaptic active zone protein that can be manipulated to enhance axon regeneration without sacrificing the function of the repaired axons. HighlightsO_LIClarinet/CLA-1 is a robust inhibitor of C. elegans GABAergic axon regeneration C_LIO_LILoss of CLA-1 function improves both axon regeneration and functional repair C_LIO_LICLA-1 isoforms differentially regulate axon regeneration and synaptic transmission C_LIO_LICLA-1 regulates axon regeneration via microtubule minus-end protein PTRN-1/Patronin C_LIO_LICLA-1 knockdown improves cargo trafficking during the early injury response C_LI

neuroscience↗

bioRxiv2024

Light tunes a novel long-term threat avoidance behavior

Animals must constantly scan their environment for imminent threats to their safety. However, they must also integrate their past experiences across long timescales to assess the potential recurrence of new threats. Though visual inputs are critical for the detection of environmental danger, whether and how visual information shapes an animals assessment of whether a new threat is likely to reappear in a given context is unknown. Using a novel behavioral assessment of long-term threat avoidance behavior, we find that animals will avoid a familiar location where they previously experienced a single exposure to an innately threatening visual stimulus. This avoidance behavior is highly sensitive and lasts for multiple days. Intriguingly, we find that the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells tune this behavior via a perihabenular-nucleus accumbens circuit distinct from the canonical visual threat detection circuits. These findings define a specific retinal cell type driving a new long-term threat avoidance behavior driven by prior visual experience.

neuroscience↗

bioRxiv2022

Geometric effects in gas vesicle buckling under ultrasound

Acoustic reporter genes based on gas vesicles (GVs) have enabled the use of ultrasound to noninvasively visualize cellular function in vivo. The specific detection of GV signals relative to background acoustic scattering in tissues is facilitated by nonlinear ultrasound imaging techniques taking advantage of the sonomechanical buckling of GVs. However, the effect of geometry on the buckling behavior of GVs under exposure to ultrasound has not been studied. To understand such geometric effects, we developed computational models of GVs of various lengths and diameters and used finite element simulations to predict their threshold buckling pressures and post-buckling deformations. We demonstrated that the GV diameter has an inverse cubic relation to the threshold buckling pressure, whereas length has no substantial effect. To complement these simulations, we experimentally probed the effect of geometry on the mechanical properties of GVs and the corresponding nonlinear ultrasound signals. The results of these experiments corroborate our computational predictions. This study provides fundamental insights into how geometry affects the sonomechanical properties of GVs, which, in turn, can inform further engineering of these nanostructures for high-contrast, nonlinear ultrasound imaging. STATEMENT OF SIGNIFICANCEGas vesicles (GVs) are an emerging class of genetically encodable and engineerable imaging agents for ultrasound whose sonomechanical buckling generates nonlinear contrast to enable sensitive and specific imaging in highly scattering biological systems. Though the effect of protein composition on GV buckling has been studied, the effect of geometry has not previously been addressed. This study reveals that geometry, especially GV diameter, significantly alters the threshold acoustic pressures required to induce GV buckling. Our computational predictions and experimental results provide fundamental understanding of the relationship between GV geometry and buckling properties and underscore the utility of GVs for nonlinear ultrasound imaging. Additionally, our results provide suggestions to further engineer GVs to enable in vivo ultrasound imaging with greater sensitivity and higher contrast.

biophysics↗

bioRxiv2022

Vertical gradients in physiological function and resource allocation of white spruce diverge at the northern- and southern-most range extremes

Light availability drives vertical canopy gradients in photosynthetic functioning and carbon (C) balance, yet patterns of variability in these gradients remain unclear. We measured light availability, photosynthetic CO2 and light response curves, foliar C, nitrogen (N) and pigment concentrations, and the photochemical reflectance index (PRI) on upper and lower canopy needles of white spruce trees (Picea glauca) at the species northern and southern range extremes. We combined our photosynthetic data with previously published respiratory data to compare and contrast canopy C balance between latitudinal extremes. We found steep canopy gradients in irradiance, photosynthesis, and leaf traits at the southern range limit, but a lack of variation across canopy positions at the northern range limit. Thus, unlike many tree species from tropical to mid-latitude forests, high latitude trees may not require vertical gradients of metabolic activity to optimize photosynthetic C gain. Consequently, accounting for self-shading is less critical for predicting gross primary productivity at northern relative to southern latitudes. Northern trees also had a significantly smaller net positive leaf C balance than southern trees suggesting that, regardless of canopy position, low photosynthetic rates coupled with high respiratory costs may ultimately constrain the northern range limit of this widely distributed boreal species. SUMMARY STATEMENTCanopy gradients in photosynthetic capacity of white spruce diminish at high compared to low latitudes. Low carbon balance in high latitude trees may determine the extent of northern treeline.

ecology↗

bioRxiv2019

Activation of Smad 2/3 signaling by low shear stress mediates artery inward remodeling

RationaleBlood vessel remodeling in response to changes in tissue demand is an important aspect of fitness and is often compromised in vascular disease. Endothelial cell (EC) sensing of fluid shear stress (FSS) governs vessel remodeling to maintain FSS at a specific magnitude or set point in healthy vessels.\n\nObjectiveThe purpose of this study was to understand how shear stress-regulated Smad 2/3 contributes to artery remodeling.\n\nMethods and ResultsWe found that shear stress induces Smad 2/3 phosphorylation, nuclear translocation, and gene expression in ECs. Nuclear translocation and gene expression are maximal at low and decrease at high FSS. Reducing flow in the mouse carotid by ligation of branch vessels induces Smad2 nuclear localization in vivo. Activation of Smad 2/3 by FSS requires the Type I TGF{beta} family receptor Alk5 and the transmembrane protein Neuropilin-1. Flow activation of Smad 2/3 is mediated by increased sensitivity to BMP9 but not BMP10 or TGF{beta}. By contrast, flow activation of Smad 1/5 is maximal at physiological FSS and requires BMP9 or 10 binding to Alk1 and Endoglin. EC-specific deletion of Alk5 in mice blocks low flow-induced inward remodeling after carotid ligation.\n\nConclusionsTogether, these data elucidate a novel pathway that mediates low flow-induced inward artery remodeling. These results may be relevant to inward remodeling in diseased vessels where Smad 2/3 is activated by pathological stimuli.

cell biology↗