Biology subjects

Lobb-Rabe, M.

Publications and source records attributed to Lobb-Rabe, M..

5 recordsLinked to original sources

bioRxiv2023

Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death

Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the cell death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their axon terminal size and activity. We termed this compensation as cross-neuron plasticity, and in this study, we demonstrated that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required in glial cells. Surprisingly, overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. Synaptic plasticity normally declines as animals age, but in our system, functional cross-neuron plasticity can be induced at different time points, whereas structural cross-neuron plasticity can only be induced at early stages. Our work uncovers a novel role for glial Draper signaling in cross-neuron plasticity that may enhance nervous system function during neurodegeneration and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons.

neuroscience↗

bioRxiv2023

Neuronal wiring receptors Dprs and DIPs are GPI anchored and this modification contributes to their cell surface organization

The Drosophila Dpr and DIP proteins belong to the immunoglobulin superfamily of cell surface proteins (CSPs). Their hetero- and homophilic interactions have been implicated in a variety of neuronal functions, including synaptic connectivity, cell survival, and axon fasciculation. However, the signaling pathways underlying these diverse functions are unknown. To gain insight into Dpr-DIP signaling, we sought to examine how these CSPs are associated with the membrane. Specifically, we asked whether Dprs and DIPs are integral membrane proteins or membrane anchored through the addition of glycosylphosphatidylinositol (GPI) linkage. We demonstrate that Dprs and DIPs are GPI anchored to the membrane of insect cells and validate these findings for some family members in vivo using Drosophila larvae, where GPI anchor cleavage results in loss of surface labeling. Additionally, we show that GPI cleavage abrogates aggregation of insect cells expressing cognate Dpr-DIP partners. To test if the GPI anchor affects Dpr-DIP localization, we replaced it with a transmembrane domain and observed perturbation of sub-cellular localization on motor neurons and muscles. These data suggest that membrane anchoring of Dprs and DIPs through GPI linkage is required for localization and that Dpr-DIP intracellular signaling likely requires transmembrane co-receptors.

neuroscience↗

bioRxiv2021

Systematic expression profiling of dprs and DIPs reveals cell surface codes in Drosophila larval peripheral neurons

In complex nervous systems, neurons must identify their correct partners to form synaptic connections. The prevailing model to ensure correct recognition posits that cell surface proteins (CSPs) in individual neurons act as identification tags. Thus, knowing what cells express which CSPs would provide insights into neural development, synaptic connectivity, and nervous system evolution. Here, we investigated expression of dprs and DIPs, two CSP subfamilies belonging to the immunoglobulin superfamily (IgSF), in Drosophila larval motor neurons (MNs), sensory neurons (SNs), peripheral glia and muscles using a collection of GAL4 driver lines. We found that dprs are more broadly expressed than DIPs in MNs and SNs, and each examined neuron expresses a unique combination of dprs and DIPs. Interestingly, many dprs and DIPs are not robustly expressed, but instead, are found in gradient and temporal expression patterns. Hierarchical clustering showed a similar expression pattern of dprs and DIPs in neurons from the same type and with shared synaptic partners, suggesting these CSPs may facilitate synaptic wiring. In addition, the unique expression patterns of dprs and DIPs revealed three uncharacterized MNs - MN23-Ib, MN6-Ib (A2) and MN7-Ib (A2). This study sets the stage for exploring the functions of dprs and DIPs in Drosophila MNs and SNs and provides genetic access to subsets of neurons.

neuroscience↗

bioRxiv2020

Structural and functional synaptic plasticity induced by convergent synapse loss requires co-innervation in the Drosophila neuromuscular circuit

Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each others structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is the Drosophila larval neuromuscular junction where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s motor neurons. We surveyed synapses on multiple muscles for this reason. Here, we identified a cell-specific promoter to ablate 1s MNs after innervation. Additionally, we genetically blocked 1s innervation. Then we measured 1b MN structural and functional responses using electrophysiology and microscopy. For all muscles, 1s MN ablation resulted in 1b MN synaptic expansion and increased basal neurotransmitter release. This demonstrates that 1b MNs can compensate for the loss of convergent inputs. However, only a subset of 1b MNs showed compensatory evoked activity, suggesting spontaneous and evoked plasticity are independently regulated. Finally, we used DIP- mutants that block 1s MN synaptic contacts; this eliminated robust 1b synaptic plasticity, raising the possibility that muscle co-innervation may define an activity "set point" that is referenced when subsequent synaptic perturbations occur. This model can be tested in more complex circuits to determine if co-innervation is fundamental for input-specific plasticity. SIGNIFICANCE STATEMENTIn complex neural circuits, multiple converging inputs contribute to the output of each target cell. Thus, each input must be regulated, but whether adjacent inputs contribute to this regulation is unclear. To examine input-specific synaptic plasticity in a structurally and functionally tractable system, we turn to the Drosophila neuromuscular circuit. Each muscle is innervated by a unique pair of motor neurons. Removal of one neuron after innervation causes the adjacent neuron to increase synaptic outgrowth and functional output. However, this is not a general feature since each MN differentially compensates. Also, robust compensation requires co-innervation by both neurons. Understanding how neurons respond to perturbations in adjacent neurons will provide insight into nervous system plasticity in both healthy and diseased states.

neuroscience↗

bioRxiv2019

How prolonged expression of Hunchback, a temporal transcription factor, re-wires locomotor circuits

AbstractIn many CNS regions, neuronal birth timing is associated with circuit membership. In Drosophila larvae, we show U motor neurons are a temporal cohort--a set of non-identical, contiguously-born neurons from a single neuronal stem cell that contribute to the same circuit. We prolong expression of a temporal transcription factor, Hunchback, to increase the number of U motor neurons with early-born molecular identities. On the circuit level, this expands and re-wires the U motor neuron temporal cohort. On the cell biological level, we find novel roles for Hunchback in motor neuron target selection, neuromuscular synapse formation, dendrite morphogenesis, and behavior. These data provide insight into the relationship between stem cell and circuit, show that Hunchback is a potent regulator of circuit assembly, and suggest that temporal transcription factors are molecules that could be altered during evolution or biomedical intervention for the generation of novel circuits.

developmental biology↗