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PLoS Genetics Oct 2022Axon and dendrite development require the cooperation of actin and microtubule cytoskeletons. Microtubules form a well-organized network to direct polarized trafficking...
Axon and dendrite development require the cooperation of actin and microtubule cytoskeletons. Microtubules form a well-organized network to direct polarized trafficking and support neuronal processes formation with distinct actin structures. However, it is largely unknown how cytoskeleton regulators differentially regulate microtubule organization in axon and dendrite development. Here, we characterize the role of actin regulators in axon and dendrite development and show that the RacGEF TIAM-1 regulates dendritic patterns through its N-terminal domains and suppresses axon growth through its C-terminal domains. TIAM-1 maintains plus-end-out microtubule orientation in posterior dendrites and prevents the accumulation of microtubules in the axon. In somatodendritic regions, TIAM-1 interacts with UNC-119 and stabilizes the organization between actin filaments and microtubules. UNC-119 is required for TIAM-1 to control axon growth, and its expression levels determine axon length. Taken together, TIAM-1 regulates neuronal microtubule organization and patterns axon and dendrite development respectively through its different domains.
Topics: Dendrites; Actins; Axons; Microtubules; Neurogenesis
PubMed: 36223408
DOI: 10.1371/journal.pgen.1010454 -
Neural Development Jul 2021Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate...
BACKGROUND
Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood.
METHODS
We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP.
RESULTS
We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width ("swellings") give rise to filopodia to facilitate a "rapid growth and pause" mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth.
CONCLUSIONS
We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate "swellings" on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor.
Topics: Actins; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Dendrites; Membrane Proteins; Nerve Tissue Proteins; Polymerization
PubMed: 34281597
DOI: 10.1186/s13064-021-00154-0 -
Neuroscience May 2022Half a century since their discovery by Llinás and colleagues, dendritic spikes have been observed in various neurons in different brain regions, from the neocortex and... (Review)
Review
Half a century since their discovery by Llinás and colleagues, dendritic spikes have been observed in various neurons in different brain regions, from the neocortex and cerebellum to the basal ganglia. Dendrites exhibit a terrifically diverse but stereotypical repertoire of spikes, sometimes specific to subregions of the dendrite. Despite their prevalence, we only have a glimpse into their role in the behaving animal. This article aims to survey the full range of dendritic spikes found in excitatory and inhibitory neurons, compare themin vivoversusin vitro, and discuss new studies describing dendritic spikes in the human cortex. We focus on neocortical and hippocampal neurons and present a roadmap to identify and understand the broader role of dendritic spikes in single-cell computation.
Topics: Action Potentials; Animals; Dendrites; Mammals; Neocortex; Neurons; Pyramidal Cells
PubMed: 35182699
DOI: 10.1016/j.neuroscience.2022.02.009 -
Scientific Reports Dec 2022Neurons are connected by complex branching processes-axons and dendrites-that process information for organisms to respond to their environment. Classifying neurons...
Neurons are connected by complex branching processes-axons and dendrites-that process information for organisms to respond to their environment. Classifying neurons according to differences in structure or function is a fundamental part of neuroscience. Here, by constructing biophysical theory and testing against empirical measures of branching structure, we develop a general model that establishes a correspondence between neuron structure and function as mediated by principles such as time or power minimization for information processing as well as spatial constraints for forming connections. We test our predictions for radius scale factors against those extracted from neuronal images, measured for species that range from insects to whales, including data from light and electron microscopy studies. Notably, our findings reveal that the branching of axons and peripheral nervous system neurons is mainly determined by time minimization, while dendritic branching is determined by power minimization. Our model also predicts a quarter-power scaling relationship between conduction time delay and body size.
Topics: Animals; Physical Phenomena; Axons; Neurons; Peripheral Nervous System; Cetacea; Dendrites
PubMed: 36460669
DOI: 10.1038/s41598-022-24813-2 -
Current Opinion in Cell Biology Oct 2023Dendrites are intricately designed neuronal compartments that play a vital role in the gathering and processing of sensory or synaptic inputs. Their diverse and... (Review)
Review
Dendrites are intricately designed neuronal compartments that play a vital role in the gathering and processing of sensory or synaptic inputs. Their diverse and elaborate structures are distinct features of neuronal organization and function. Central to the generation of these dendritic arbors is the neuronal cytoskeleton. In this review, we delve into the current progress toward our understanding of how dendrite arbors are generated and maintained, focusing on the role of the actin and microtubule cytoskeleton.
Topics: Actins; Dendrites; Microtubules; Cytoskeleton; Neurons
PubMed: 37544207
DOI: 10.1016/j.ceb.2023.102214 -
Genes Apr 2020The pseudostratified olfactory epithelium (OE) may histologically appear relatively simple, but the cytological relations among its cell types, especially those between... (Review)
Review
The pseudostratified olfactory epithelium (OE) may histologically appear relatively simple, but the cytological relations among its cell types, especially those between olfactory receptor neurons (ORNs) and olfactory sustentacular cells (OSCs), prove more complex and variable than previously believed. Adding to the complexity is the short lifespan, persistent neurogenesis, and continuous rewiring of the ORNs. Contrary to the common belief that ORN dendrites are mostly positioned between OSCs, recent findings indicate a sustentacular cell enwrapped configuration for a majority of mature ORN dendrites at the superficial layer of the OE. After vertically sprouting out from the borderlines between OSCs, most of the immature ORN dendrites undergo a process of sideways migration and terminal maturation to become completely invaginated into and enwrapped by OSCs. Trailing the course of the dendritic sideways migration is the mesodendrite (mesentery of the enwrapped dendrite) made of closely apposed, cell junction connected plasma membrane layers of neighboring folds of the host sustentacular cell. Only a minority of the mature ORN dendrites at the OE apical surface are found at the borderlines between OSCs (unwrapped). Below I give a brief update on the cytoarchitectonic relations between the ORNs and OSCs of the OE. Emphasis is placed on the enwrapment of ORN dendrites by OSCs, on the sideways migration of immature ORN dendrites after emerging from the OE surface, and on the terminal maturation of the ORNs. Functional implications of ORN dendrite enwrapment and a comparison with myelination or Remak's bundling of axons or axodendrites in the central and peripheral nervous system are also discussed.
Topics: Axons; Dendrites; Humans; Neurogenesis; Olfactory Mucosa; Olfactory Receptor Neurons; Receptors, Odorant; Smell
PubMed: 32365880
DOI: 10.3390/genes11050493 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... May 2020Neurons are the structural and functional unit of the nervous system. Precisely regulated dendrite morphogenesis is the basis of neural circuit assembly. Numerous... (Review)
Review
Neurons are the structural and functional unit of the nervous system. Precisely regulated dendrite morphogenesis is the basis of neural circuit assembly. Numerous studies have been conducted to explore the regulatory mechanisms of dendritic morphogenesis. According to their action regions, we divide them into two categories: the intrinsic and extrinsic regulators of neuronal dendritic morphogenesis. Intrinsic factors are cell type-specific transcription factors, actin polymerization or depolymerization regulators and regulators of the secretion or endocytic pathways. These intrinsic factors are produced by neuron itself and play an important role in regulating the development of dendrites. The extrinsic regulators are either secreted proteins or transmembrane domain containing cell adhesion molecules. They often form receptor-ligand pairs to mediate attractive or repulsive dendritic guidance. In this review, we summarize recent findings on the intrinsic and external molecular mechanisms of dendrite morphogenesis from multiple model organisms, including , and mice. These studies will provide a better understanding on how defective dendrite development and maintenance are associated with neurological diseases.
Topics: Animals; Caenorhabditis elegans; Dendrites; Mice; Morphogenesis; Nervous System Diseases; Neurons; Transcription Factors
PubMed: 32621417
DOI: 10.3785/j.issn.1008-9292.2020.02.09 -
The Journal of Cell Biology Jan 2023Disruptions in membrane trafficking are associated with neurodevelopmental disorders, but underlying pathological mechanisms remain largely unknown. In this issue,...
Disruptions in membrane trafficking are associated with neurodevelopmental disorders, but underlying pathological mechanisms remain largely unknown. In this issue, O'Brien et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202112108) show how GARP regulates sterol transfer critical for remodeling of dendrites in flies.
Topics: Dendrites; Membranes; Neurodevelopmental Disorders; Sterols; Membrane Proteins
PubMed: 36547519
DOI: 10.1083/jcb.202211072 -
Journal of Neurophysiology Jan 2021Dendritic spikes in thin dendritic branches (basal and oblique dendrites) are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot...
Dendritic spikes in thin dendritic branches (basal and oblique dendrites) are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially restricted glutamatergic inputs. Local dendritic potentials lasted 200-500 ms and propagated to the cell body, where they caused sustained 10- to 20-mV depolarizations. Plateau potentials propagating from dendrite to soma and action potentials propagating from soma to dendrite created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and backpropagating action potentials, superimposed on each other. Our model replicated these voltage waveforms across a gradient of glutamatergic stimulation intensities. The model then predicted that somatic input resistance () and membrane time constant (tau) may be reduced during dendritic plateau potential. We then tested these model predictions in real neurons and found that the model correctly predicted the direction of and tau change but not the magnitude. In summary, dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state ("prepared state"), characterized by depolarized membrane potential and smaller but faster membrane responses. The prepared state provides a time window of 200-500 ms, during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles. In cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials with voltage imaging and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state: a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.
Topics: Action Potentials; Animals; Cerebral Cortex; Dendrites; Female; Glutamic Acid; Male; Models, Neurological; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Synaptic Potentials
PubMed: 33085562
DOI: 10.1152/jn.00734.2019 -
Developmental Cell Jul 2023In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse...
In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. We find that spontaneous activity generated within the olfactory bulb is essential. We show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. Our results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.
Topics: Dendrites; Olfactory Bulb; Synapses; Neurons; Cell Differentiation
PubMed: 37290446
DOI: 10.1016/j.devcel.2023.05.004