Publications by authors named "Wesley B Grueber"
Mitofusin-2 (MFN2), a large GTPase residing in the mitochondrial outer membrane and mutated in Charcot-Marie-Tooth type 2 disease (CMT2A), is a regulator of mitochondrial fusion and tethering with the ER. The role of MFN2 in mitochondrial transport has however remained elusive. Like MFN2, acetylated microtubules play key roles in mitochondria dynamics.
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- Internal sensory neurons are crucial for monitoring the body's chemical and physical state, helping maintain homeostasis and survival.
- The study focuses on tracheal dendrite (td) neurons in larvae, which are responsive to changes in oxygen and carbon dioxide levels, providing insights into how these neurons sense their environment.
- Key findings reveal that two types of guanylyl cyclases (Gyc88E/Gyc89Db) are essential for detecting low oxygen, while a specific gustatory receptor (Gr28b) is critical for sensing carbon dioxide, especially when larvae are in feeding conditions like burrowing.
When threatened by dangerous or harmful stimuli, animals engage in diverse forms of rapid escape behaviors. In larvae, one type of escape response involves C-shaped bending and lateral rolling followed by rapid forward crawling. The sensory circuitry that promotes larval escape has been extensively characterized; however, the motor programs underlying rolling are unknown.
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- * Mitofusin-2 (MFN2), a protein involved in mitochondrial functions and linked to Charcot-Marie-Tooth disease, was found to help recruit the enzyme that acetylates alpha-tubulin, which is crucial for mitochondrial transport.
- * Mutations in MFN2 related to CMT2A may lead to axonal degeneration by hindering the process that allows the release of the acetylation enzyme, implicating disturbances in tubulin acetylation as a factor in the disease.
Synaptic connections between neurons are often formed in precise subcellular regions of dendritic arbors with implications for information processing within neurons. Cell-cell interactions are widely important for circuit wiring; however, their role in subcellular specificity is not well understood. We studied the role of axon-axon interactions in precise targeting and subcellular wiring of Drosophila somatosensory circuitry.
View Article and Find Full Text PDFAxon and dendrite placement and connectivity is guided by a wide range of secreted and surface molecules in the developing nervous system. Nevertheless, the extraordinary complexity of connections in the brain requires that this repertoire be further diversified to precisely and uniquely regulate cell-cell interactions. One important mechanism for molecular diversification is alternative splicing.
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- The study investigates how Drosophila larvae escape from threats using a unique rolling behavior marked by C-shaped bending and rapid forward movement.
- Researchers used advanced imaging techniques to analyze muscle activity during this rolling escape, revealing that muscle contractions progress circumferentially rather than in a sequential manner.
- The findings highlight the importance of specific neuron connections and suggest that certain premotor neurons play a key role in coordinating the muscle patterns necessary for effective rolling escape behavior.
Article Synopsis
- - Disruptions in how membranes transport materials are linked to neurodevelopmental disorders, but the reasons behind this aren't fully understood.
- - O'Brien et al. (2023) investigate the role of a protein called GARP in regulating the transfer of sterols, which are important for dendrite remodeling in fruit flies.
- - Their findings provide insight into the mechanisms of membrane trafficking and its potential impact on understanding neurodevelopmental disorders.
The Immunoglobulin Superfamily Member Basigin Is Required for Complex Dendrite Formation in .
Front Cell Neurosci
November 2021
Coordination of dendrite growth with changes in the surrounding substrate occurs widely in the nervous system and is vital for establishing and maintaining neural circuits. However, the molecular basis of this important developmental process remains poorly understood. To identify potential mediators of neuron-substrate interactions important for dendrite morphogenesis, we undertook an expression pattern-based screen in larvae, which revealed many proteins with expression in dendritic arborization (da) sensory neurons and in neurons and their epidermal substrate.
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- Chemotherapy-induced peripheral neuropathy (CIPN) is a common and poorly understood side effect of cancer treatment that affects pain-sensing nerve cells, leading to degeneration and altered functioning.
- In a study using adult mouse sensory neurons, researchers found that the chemotherapy drug paclitaxel caused damage to these neurons and reduced their ability to respond to heat, but overexpression of integrins helped protect against this damage.
- The study highlights that paclitaxel disrupts the recycling of integrins, which are vital for neuron maintenance, and suggests that restoring integrin function may offer a potential therapeutic approach for mitigating CIPN effects.
Article Synopsis
- The text presents a new technique for editing Drosophila (fruit fly) genomic sequences at specific sites without leaving scars from the genetic modifications.
- It involves a two-step process using phiC31 integrase for precise integration and homing nucleases to fix any duplications, which results in modified gene alleles.
- The method includes dominant markers to easily identify successful genetic modifications and can potentially be applied to other species beyond Drosophila.
Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy.
Proc Natl Acad Sci U S A
January 2021
Article Synopsis
- The study investigates how the chemotherapy drug bortezomib causes peripheral neuropathy by affecting tubulin stability in sensory neurons.
- It finds that bortezomib leads to increased levels of delta 2 tubulin (D2), particularly in unmyelinated fibers, which is linked to neuronal damage.
- Reducing D2 levels in neurons appears to prevent axonal degeneration and restore mitochondrial function, suggesting that targeting D2 may help mitigate side effects from bortezomib.
Article Synopsis
- Proprioceptors are crucial for sensing body position and enabling coordinated movement, but how animals with flexible skeletons encode their body positions is not well understood.
- In this study, researchers used advanced SCAPE microscopy to observe the activity of proprioceptors in crawling Drosophila larvae, revealing that most neurons activated during segment contraction, while one subtype responded to extension.
- The findings highlight the sequential activation of different proprioceptor types during movement, suggesting they play distinct roles in monitoring body deformation, and demonstrate the effectiveness of SCAPE microscopy for exploring neural activity in live animals.
Article Synopsis
- - The text discusses how rapid escape behaviors in response to harmful stimuli are crucial for survival, highlighting a lack of understanding regarding the mechanisms linking stimuli to coordinated responses.
- - Researchers identified specific interneurons called Down-and-Back (DnB) neurons in larvae that are activated by harmful heat and are critical for effective escape behaviors, such as body bending and rolling.
- - DnB neurons connect with nociceptive and mechanosensory neurons and interact with pre-motor circuits, coordinating the escape responses by promoting activity in Goro neurons, which are necessary for rolling movements.
Article Synopsis
- The study explores internal sensory neurons, specifically tracheal dendrite (td) neurons, that sense the body's internal state and play a key role in maintaining physiological balance.
- It identifies two distinct classes of td neurons based on their axon projections: one class targets the subesophageal zone (SEZ) in the brain, while the other class connects to the ventral nerve cord (VNC).
- The research highlights the role of a transcription factor called Pdm3 in guiding the axon targeting process of these neurons, indicating potential mechanisms behind how sensory neurons develop and function in monitoring internal conditions.
Article Synopsis
- Fragile X syndrome is the leading known genetic cause of autism and is linked to the loss of the FMR1 protein, which is crucial for RNA binding.
- Research indicates that individuals with Fragile X syndrome have immune system defects, showing increased susceptibility to infections and reduced ability to clear bacteria by immune cells.
- The study reveals that FMR1 is important for the functioning of immune cells in both body and brain, impacting processes like neuronal clearance after injury and brain development essential for learning and memory.
Article Synopsis
- * In Drosophila, the growth of sensory neuron dendrites is controlled by certain proteins (Pdm1, Pdm2, Cut, Scalloped, and Vestigial) that work together to limit dendrite growth, resulting in varied neuron types.
- * The balance of these proteins influences how complex or simple the dendritic structures are, with specific interactions determining the final morphology of different sensory neurons within the body.
Article Synopsis
- A new microscopy technique called SCAPE (Swept, confocally-aligned planar excitation) enables ultra-fast volumetric imaging of live samples, overcoming limitations of traditional methods.
- Unlike confocal and two-photon microscopy, SCAPE uses a single-objective setup with an angled light-sheet, allowing for high-speed imaging without the need for sample movement.
- This method was demonstrated by imaging real-time neuronal activity in the brains of awake mice and in freely moving larvae, showcasing its potential for advanced biomedical research.
Development of the embryonic and larval peripheral nervous system of Drosophila.
Wiley Interdiscip Rev Dev Biol
January 2015
Article Synopsis
- The PNS in embryonic and larval Drosophila is made up of various sensory neurons that have consistent locations and shapes, making it an ideal system for studying neural development.
- Research on Drosophila's PNS has revealed important mechanisms of how sensory neurons are formed, how they divide asymmetrically, and how their dendrites develop, influenced by several factors.
- The axons of sensory neurons exhibit specific termination patterns in the central nervous system, guided by signaling molecules, which are essential for the organism's coordinated movements and behaviors.
Article Synopsis
- Environmental and cellular signals influence how dendrites grow and find their targets, but the specific signals from the substrate are not well understood.
- Research by Dong et al. and Salzberg et al. has identified a complex involving three components that helps transmit signals from the substrate.
- This complex is crucial for guiding the development of intricate dendrite patterns in the organism C. elegans.
Article Synopsis
- - Self-avoidance is a phenomenon where neurites from the same neuron avoid each other, seen in both vertebrates and invertebrates, and is crucial for proper neural network formation.
- - In Drosophila, this self-avoidance is controlled by a diverse set of cell recognition molecules called Dscam1, which allows neurons to express different isoforms that enable them to distinguish between their own processes and those of others.
- - Research also indicates that in mice, a similar mechanism is facilitated by clustered protocadherins, suggesting that this ability to avoid self-interference has evolved across different species using comparable molecular strategies.
Article Synopsis
- Dendrites, the branching extensions of neurons, have a self-avoidance behavior that prevents them from overlapping with their own branches while allowing them to interact with branches from nearby neurons.
- A new study by Lefebvre and his team identifies clustered protocadherins as the key molecules responsible for this recognition process in vertebrates.
- This finding enhances our understanding of how neurons organize themselves in the brain, which is important for proper neural function and development.
Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization sensory neurons can be positioned either at the basal surface of epidermal cells, or enclosed within epidermal invaginations.
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- * Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) plays a crucial role in self-recognition and repulsion, preventing unwanted overlap of dendrites and axons in neurons.
- * Dscam1 balances external signals from Netrin-B and its receptor, Frazzled, ensuring proper dendritic coverage and preventing excessive accumulation at target sites, indicating its importance in neural circuit formation.