Start early and pack light: Collaborative adventures in theory and experiment

Seminars in Cell and Developmental Biology · 2025-07-26

Visual input drives diverse ER calcium signals in neurons <i>in vivo</i>

bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-22

ABSTRACT The endoplasmic reticulum (ER) has long been thought to shape calcium signals in neurons, but stimulus-driven ER calcium fluctuations have not been directly measured in vivo . To measure neuronal ER calcium signals in vivo , we paired visual stimulus presentation with two photon imaging of ER and cytosolic calcium reporters in four different cell types in the Drosophila visual system. We found that visual input elicits diverse ER calcium signals, with the ER acting as a calcium sink or source depending on the cell type, subcellular compartment (dendrite versus axon), and type of visual stimulus. ER calcium signals were not simply a reflection of cytosolic signals, indicating that the ER, rather than acting as a passive calcium buffer, actively processes calcium signals in neurons in a context-specific fashion. Thus, ER-based signal processing may contribute to functional diversity across neuronal cell types, thereby enhancing the computational capacity of neural circuits.

<i>Drosophila</i> HS dendrites are resilient to adult-onset deficits in mitochondrial dynamics

bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-09

ABSTRACT Mitochondrial transport, fusion, and fission are necessary for neuronal development, but the role of mitochondrial dynamics in neuronal maintenance remains unclear. In this work, we employed functional in vivo imaging of neurons in the Drosophila visual system, HS (“horizontal system”) cells, to determine how adult-onset deficits in mitochondrial dynamics affect mitochondrial localization, local regulation of ATP, and dendrite maintenance. In mature HS neurons, inhibition of mitochondrial transport or fusion depleted mitochondria from the dendrite over time but, surprisingly, had no effect on dendrite morphology. Moreover, adult-restricted mitochondrial mis- localization affected neither visual stimulus-driven dendritic calcium responses nor local, dynamic regulation of ATP levels. In contrast, when induced during development, the same perturbations caused mitochondrial mis-localization, loss of dendrite complexity, abrogation of stimulus-locked calcium responses and ATP fluctuations, and age-dependent dendrite degeneration. Thus, although mitochondrial dynamics are necessary during neuronal development, mature dendrites are capable of maintaining form and function in vivo in the absence of properly-positioned mitochondria.

Dendrite architecture determines mitochondrial distribution patterns in vivo

Cell Reports · 2024 · 11 citations

• Biology
• Biophysics
• Cell biology

Neuronal morphology influences synaptic connectivity and neuronal signal processing. However, it remains unclear how neuronal shape affects steady-state distributions of organelles like mitochondria. In this work, we investigated the link between mitochondrial transport and dendrite branching patterns by combining mathematical modeling with in vivo measurements of dendrite architecture, mitochondrial motility, and mitochondrial localization patterns in Drosophila HS (horizontal system) neurons. In our model, different forms of morphological and transport scaling rules-which set the relative thicknesses of parent and daughter branches at each junction in the dendritic arbor and link mitochondrial motility to branch thickness-predict dramatically different global mitochondrial localization patterns. We show that HS dendrites obey the specific subset of scaling rules that, in our model, lead to realistic mitochondrial distributions. Moreover, we demonstrate that neuronal activity does not affect mitochondrial transport or localization, indicating that steady-state mitochondrial distributions are hard-wired by the architecture of the neuron.

Dendrite architecture determines mitochondrial distribution patterns <i>in vivo</i>

bioRxiv (Cold Spring Harbor Laboratory) · 2022-07-03 · 4 citations

SUMMARY Mitochondria are critical for neuronal function and must be reliably distributed through complex neuronal architectures. By quantifying in vivo mitochondrial transport and localization patterns in the dendrites of Drosophila visual system neurons, we show that mitochondria make up a dynamic system at steady-state, with significant transport of individual mitochondria within a stable global pattern. Mitochondrial motility patterns are unaffected by visual input, suggesting that neuronal activity does not directly regulate mitochondrial localization in vivo . Instead, we present a mathematical model in which four simple scaling rules enable the robust self-organization of the mitochondrial population. Experimental measurements of dendrite morphology validate key model predictions: to maintain equitable distribution of mitochondria across asymmetrically branched subtrees, dendritic branch points obey a parent-daughter power law that preserves cross-sectional area, and thicker trunks support proportionally bushier subtrees. Altogether, we propose that “housekeeping” requirements, including the need to maintain steady-state mitochondrial distributions, impose constraints on neuronal architecture.

Cell Mechanics at the Rear Act to Steer the Direction of Cell Migration

Cell Systems · 2020 · 46 citations

• Computer Science
• Cell biology
• Mechanics

Modeling cell turning by mechanics at the cell rear

bioRxiv (Cold Spring Harbor Laboratory) · 2020-06-04 · 2 citations

Abstract In this study, we explore a simulation of a mechanical model of the keratocyte lamellipodium as previously tested and calibrated for straight steady-state motility [1] and for the process of polarization and motility initiation [2]. In brief, this model uses the balance of three essential forces (myosin contraction, adhesive drag and actin network viscosity) to determine the cell’s mechanical behavior. Cell shape is set by the balance between the actin polymerization-driven protrusion at the cell boundary and myosin-driven retraction of the actin-myosin network. In the model, myosin acts to generate contractile stress applied to a viscous actin network with viscous resistance to actin flow created by adhesion to the substrate. Previous study [3] demonstrated that similar simple model with uniform constant adhesion predicts a rotating behavior of the cell; however, this behavior is idealized, and does not mimic observed features of the keratocyte’s turning behavior. Our goal is to explore what are the consequences of introducing mechanosensitive adhesions to the model.

Experiment, theory, and the keratocyte: An ode to a simple model for cell motility

Seminars in Cell and Developmental Biology · 2019-11-09 · 38 citations

Sequential Nonlinear Filtering of Local Motion Cues by Global Motion Circuits

Neuron · 2018-09-13 · 23 citations

Cell Mechanics at the Rear Act To Steer the Direction of Cell Migration

bioRxiv (Cold Spring Harbor Laboratory) · 2018-10-15 · 13 citations

Summary Motile cells navigate complex environments by changing their direction of travel, generating left-right asymmetries in their mechanical subsystems to physically turn. Currently little is known about how external directional cues are propagated along the length scale of the whole cell and integrated with its force-generating apparatus to steer migration mechanically. We examine the mechanics of spontaneous cell turning in fish epidermal keratocytes and find that the mechanical asymmetries responsible for turning behavior predominate at the rear of the cell, where there is asymmetric centripetal actin flow. Using experimental perturbations we identify two linked feedback loops connecting myosin II contractility, adhesion strength and actin network flow in turning cells that are sufficient to recreate observed cell shapes and trajectories in a computational model. Surprisingly, asymmetries in actin polymerization at the cell leading edge play only a minor role in the mechanics of cell turning – that is, cells steer from the rear. Highlights Fish keratocytes can migrate with persistent angular velocity, straight or in circles. Asymmetry in protrusion at the leading edge is not sufficient to generate persistent turning. Asymmetries in myosin II contraction, actin flow and adhesion at the cell rear cause turns. Our new computational model of migration predicts observed cell trajectories.