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Proceedings of the National Academy of... Mar 2023During mitosis, cells round up and utilize the interphase adhesion sites within the fibrous extracellular matrix (ECM) as guidance cues to orient the mitotic spindles....
During mitosis, cells round up and utilize the interphase adhesion sites within the fibrous extracellular matrix (ECM) as guidance cues to orient the mitotic spindles. Here, using suspended ECM-mimicking nanofiber networks, we explore mitotic outcomes and error distribution for various interphase cell shapes. Elongated cells attached to single fibers through two focal adhesion clusters (FACs) at their extremities result in perfect spherical mitotic cell bodies that undergo significant 3-dimensional (3D) displacement while being held by retraction fibers (RFs). Increasing the number of parallel fibers increases FACs and retraction fiber-driven stability, leading to reduced 3D cell body movement, metaphase plate rotations, increased interkinetochore distances, and significantly faster division times. Interestingly, interphase kite shapes on a crosshatch pattern of four fibers undergo mitosis resembling single-fiber outcomes due to rounded bodies being primarily held in position by RFs from two perpendicular suspended fibers. We develop a cortex-astral microtubule analytical model to capture the retraction fiber dependence of the metaphase plate rotations. We observe that reduced orientational stability, on single fibers, results in increased monopolar mitotic defects, while multipolar defects become dominant as the number of adhered fibers increases. We use a stochastic Monte Carlo simulation of centrosome, chromosome, and membrane interactions to explain the relationship between the observed propensity of monopolar and multipolar defects and the geometry of RFs. Overall, we establish that while bipolar mitosis is robust in fibrous environments, the nature of division errors in fibrous microenvironments is governed by interphase cell shapes and adhesion geometries.
Topics: Cell Nucleus Division; Mitosis; Centrosome; Aircraft; Axons
PubMed: 36848565
DOI: 10.1073/pnas.2120536120 -
Frontiers in Cellular Neuroscience 2017The cerebral cortex is composed of billions of neurons that can grossly be subdivided into two broad classes: inhibitory GABAergic interneurons and excitatory... (Review)
Review
The cerebral cortex is composed of billions of neurons that can grossly be subdivided into two broad classes: inhibitory GABAergic interneurons and excitatory glutamatergic neurons. The majority of cortical neurons in mammals are the excitatory type and they are the main focus of this review article. Like many of the cells in multicellular organisms, fully differentiated neurons are both morphologically and functionally polarized. However, they go through several changes in polarity before reaching this final mature differentiated state. Neurons are derived from polarized neuronal progenitor/stem cells and their commitment to neuronal fate is decided by cellular and molecular asymmetry during their last division in the neurogenic zone. They migrate from their birthplace using so-called multipolar migration, during which they switch direction of movement several times, and repolarize for bipolar migration when the axon is specified. Therefore, neurons have to break their previous symmetry, change their morphology and adequately respond to polarizing signals during migration in order to reach the correct position in the cortex and start making connections. Finally, the dendritic tree is elaborated and the axon/dendrite morphological polarity is set. Here we will describe the function, establishment and maintenance of polarity during the different developmental steps starting from neural stem cell (NSC) division, neuronal migration and axon specification at embryonic developmental stages.
PubMed: 28670267
DOI: 10.3389/fncel.2017.00163 -
Current Opinion in Cell Biology Aug 2012In a biological sense, polarity refers to the extremity of the main axis of an organelle, cell, or organism. In neurons, morphological polarity begins with the... (Review)
Review
In a biological sense, polarity refers to the extremity of the main axis of an organelle, cell, or organism. In neurons, morphological polarity begins with the appearance of the first neurite from the cell body. In multipolar neurons, a second phase of polarization occurs when a single neurite initiates a phase of rapid growth to become the neuron's axon, while the others later differentiate as dendrites. Finally, during a third phase, axons and dendrites develop an elaborate architecture, acquiring special morphological and molecular features that commit them to their final identities. Mechanistically, each phase must be preceded by spatial restriction of growth activity. We will review recent work on the mechanisms underlying the polarized growth of neurons.
Topics: Cell Polarity; Neurites; Neurons; Organelles
PubMed: 22726583
DOI: 10.1016/j.ceb.2012.05.011 -
Current Opinion in Neurobiology Oct 2012The migration of neurons along glial fibers from a germinal zone (GZ) to their final laminar positions is essential for morphogenesis of the developing brain;... (Review)
Review
The migration of neurons along glial fibers from a germinal zone (GZ) to their final laminar positions is essential for morphogenesis of the developing brain; aberrations in this process are linked to profound neurodevelopmental and cognitive disorders. During this critical morphogenic movement, neurons must navigate complex migration paths, propelling their cell bodies through the dense cellular environment of the developing nervous system to their final destinations. It is not understood how neurons can successfully migrate along their glial guides through the myriad processes and cell bodies of neighboring neurons. Although much progress has been made in understanding the substrates (Fishell G, Hatten ME: Astrotactin provides a receptor system for CNS neuronal migration. Development 1991, 113:755; Elias LA, Wang DD, Kriegstein AR: Gap junction adhesion is necessary for radial migration in the neocortex. Nature 2007, 448:901; Anton ES, Kreidberg JA, Rakic P: Distinct functions of alpha3 and alpha. (v) integrin receptors in neuronal migration and laminar organization of the cerebral cortex. Neuron 1999, 22:277; Anton ES, Marchionni MA, Lee KF, Rakic P: Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex. Development 1997, 124:3501), guidance mechanisms (Polleux F, Whitford KL, Dijkhuizen PA, Vitalis T, Ghosh A: Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling. Development 2002, 129:3147; Zhou P, et al.: Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron 2007, 55:53; Renaud J, et al.: Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nat Neurosci 2008, 11:440), cytoskeletal elements (Schaar BT, McConnell SK: Cytoskeletal coordination during neuronal migration. Proc Natl Acad Sci U S A 2005, 102:13652; Tsai JW, Bremner KH, Vallee RB: Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat Neurosci 2007, 10:970; Solecki DJ, et al.: Myosin II motors and F-actin dynamics drive the coordinated movement of the centrosome and soma during CNS glial-guided neuronal migration. Neuron 2009, 63:63), and post-translational modifications (Patrick GN, Zhou P, Kwon YT, Howley PM, Tsai LH: p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway. J Biol Chem 1998, 273:24057; Suetsugu S, et al.: Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1. Biochem J 2004, 384:1; Karakuzu O, Wang DP, Cameron S: MIG-32 and SPAT-3A are PRC1 homologs that control neuronal migration inCaenorhabditis elegans. Development 2009, 136:943) required for neuronal migration, we have yet to elucidate how neurons regulate their cellular interactions and adhesive specificity to follow the appropriate migratory pathways. Here I will examine recent developments in our understanding of the mechanisms controlling neuronal cell adhesion and how these mechanisms interact with crucial neurodevelopmental events, such as GZ exit, migration pathway selection, multipolar-to-radial transition, and final lamination.
Topics: Animals; Cell Adhesion; Cell Movement; Humans; Neurons
PubMed: 22560352
DOI: 10.1016/j.conb.2012.04.010 -
Frontiers in Physiology 2022Endomembrane alkali cation (Na, K)/proton (H) exchangers (eNHEs) are increasingly associated with neurological disorders. These eNHEs play integral roles in regulating... (Review)
Review
Endomembrane alkali cation (Na, K)/proton (H) exchangers (eNHEs) are increasingly associated with neurological disorders. These eNHEs play integral roles in regulating the luminal pH, processing, and trafficking of cargo along the secretory (Golgi and post-Golgi vesicles) and endocytic (early, recycling, and late endosomes) pathways, essential regulatory processes vital for neuronal development and plasticity. Given the complex morphology and compartmentalization of multipolar neurons, the contribution of eNHEs in maintaining optimal pH homeostasis and cargo trafficking is especially significant during periods of structural and functional development and remodeling. While the importance of eNHEs has been demonstrated in a variety of non-neuronal cell types, their involvement in neuronal function is less well understood. In this review, we will discuss their emerging roles in excitatory synaptic function, particularly as it pertains to cellular learning and remodeling. We will also explore their connections to neurodevelopmental conditions, including intellectual disability, autism, and attention deficit hyperactivity disorders.
PubMed: 35547574
DOI: 10.3389/fphys.2022.892196 -
Cells Apr 2022Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized...
Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized compartments, such as axons and dendrites. Disruption of the Golgi apparatus (GA) secretory pathway in developing neurons alters axon/dendritic formation. Therefore, detailed knowledge of the mechanisms underlying vesicles exiting from the GA is crucial for understanding neuronal polarity. In this study, we analyzed the role of Brefeldin A-Ribosylated Substrate (CtBP1-S/BARS), a member of the C-terminal-binding protein family, in the regulation of neuronal morphological polarization and the exit of membrane proteins from the Trans Golgi Network. Here, we show that BARS is expressed during neuronal development in vitro and that RNAi suppression of BARS inhibits axonal and dendritic elongation in hippocampal neuronal cultures as well as largely perturbed neuronal migration and multipolar-to-bipolar transition during cortical development in situ. In addition, using plasma membrane (PM) proteins fused to GFP and engineered with reversible aggregation domains, we observed that expression of fission dominant-negative BARS delays the exit of dendritic and axonal membrane protein-containing carriers from the GA. Taken together, these data provide the first set of evidence suggesting a role for BARS in neuronal development by regulating post-Golgi membrane trafficking.
Topics: Axons; Golgi Apparatus; Membrane Proteins; Neurons; trans-Golgi Network
PubMed: 35455998
DOI: 10.3390/cells11081320 -
Journal of Anatomy Jan 2021The present study analyses the organization and selected neurochemical features of the claustrum and visual cortex of the sheep, based on the patterns of calcium-binding...
The present study analyses the organization and selected neurochemical features of the claustrum and visual cortex of the sheep, based on the patterns of calcium-binding proteins expression. Connections of the claustrum with the visual cortex have been studied by tractography. Parvalbumin-immunoreactive (PV-ir) and Calbindin-immunoreactive (CB-ir) cell bodies increased along the rostro-caudal axis of the nucleus. Calretinin (CR)-labeled somata were few and evenly distributed along the rostro-caudal axis. PV and CB distribution in the visual cortex was characterized by larger round and multipolar cells for PV, and more bitufted neurons for CB. The staining pattern for PV was the opposite of that of CR, which showed densely stained but rare cell bodies. Tractography shows the existence of connections with the caudal visual cortex. However, we detected no contralateral projection in the visuo-claustral interconnections. Since sheep and goats have laterally placed eyes and a limited binocular vision, the absence of contralateral projections could be of prime importance if confirmed by other studies, to rule out the role of the claustrum in stereopsis.
Topics: Animals; Calbindin 2; Calbindins; Claustrum; Female; Neural Pathways; Neurons; Parvalbumins; Sheep; Visual Cortex
PubMed: 32885430
DOI: 10.1111/joa.13302 -
Science (New York, N.Y.) Apr 2022Terreros-Roncal . investigated the impacts of human neurodegeneration on immunostainings assumed to be associated with neurogenesis. However, the study provides no...
Terreros-Roncal . investigated the impacts of human neurodegeneration on immunostainings assumed to be associated with neurogenesis. However, the study provides no evidence that putative proliferating cells are linked to neurogenesis, that multipolar nestin astrocytes are progenitors, or that mature-looking doublecortin neurons are adult-born. Their histology-marker expression differs from what is observed in species where adult hippocampal neurogenesis is well documented.
Topics: Adult; Astrocytes; Hippocampus; Humans; Neurodegenerative Diseases; Neurogenesis; Neurons
PubMed: 35420933
DOI: 10.1126/science.abn8861 -
Frontiers in Neural Circuits 2022The lateral superior olive (LSO) is a key structure in the central auditory system of mammals that exerts efferent control on cochlear sensitivity and is involved in the...
The lateral superior olive (LSO) is a key structure in the central auditory system of mammals that exerts efferent control on cochlear sensitivity and is involved in the processing of binaural level differences for sound localization. Understanding how the LSO contributes to these processes requires knowledge about the resident cells and their connections with other auditory structures. We used standard histological stains and retrograde tracer injections into the inferior colliculus (IC) and cochlea in order to characterize two basic groups of neurons: (1) Principal and periolivary (PO) neurons have projections to the IC as part of the ascending auditory pathway; and (2) lateral olivocochlear (LOC) intrinsic and shell efferents have descending projections to the cochlea. Principal and intrinsic neurons are intermixed within the LSO, exhibit fusiform somata, and have disk-shaped dendritic arborizations. The principal neurons have bilateral, symmetric, and tonotopic projections to the IC. The intrinsic efferents have strictly ipsilateral projections, known to be tonotopic from previous publications. PO and shell neurons represent much smaller populations (<10% of principal and intrinsic neurons, respectively), have multipolar somata, reside outside the LSO, and have non-topographic, bilateral projections. PO and shell neurons appear to have widespread projections to their targets that imply a more diffuse modulatory function. The somata and dendrites of principal and intrinsic neurons form a laminar matrix within the LSO and share quantifiably similar alignment to the tonotopic axis. Their restricted projections emphasize the importance of frequency in binaural processing and efferent control for auditory perception. This study addressed and expanded on previous findings of cell types, circuit laterality, and projection tonotopy in the LSO of the mouse.
Topics: Animals; Mice; Superior Olivary Complex; Olivary Nucleus; Auditory Pathways; Inferior Colliculi; Neurons; Mammals
PubMed: 36338332
DOI: 10.3389/fncir.2022.1038500 -
American Journal of Human Biology : the... 2011Von Economo neurons (VENs) are defined by their thin, elongated cell body and long dendrites projecting from apical and basal ends. These distinctive neurons are mostly... (Review)
Review
OBJECTIVES
Von Economo neurons (VENs) are defined by their thin, elongated cell body and long dendrites projecting from apical and basal ends. These distinctive neurons are mostly present in anterior cingulate (ACC) and fronto-insular (FI) cortex, with particularly high densities in cetaceans, elephants, and hominoid primates (i.e., humans and apes). This distribution suggests that VENs contribute to specializations of neural circuits in species that share both large brain size and complex social cognition, possibly representing an adaptation to rapidly relay socially-relevant information over long distances across the brain. Recent evidence indicates that unique patterns of protein expression may also characterize VENs, particularly involving molecules that are known to regulate gut and immune function.
METHODS
In this study, we used quantitative stereologic methods to examine the expression of three such proteins that are localized in VENs-activating-transcription factor 3 (ATF3), interleukin 4 receptor (IL4Rα), and neuromedin B (NMB). We quantified immunoreactivity against these proteins in different morphological classes of ACC layer V neurons of hominoids.
RESULTS
Among the different neuron types analyzed (pyramidal, VEN, fork, enveloping, and other multipolar), VENs showed the greatest percentage that displayed immunostaining. Additionally, a higher proportion of VENs in humans were immunoreactive to ATF3, IL4Rα, and NMB than in other apes. No other ACC layer V neuron type displayed a significant species difference in the percentage of immunoreactive neurons.
CONCLUSIONS
These findings demonstrate that phylogenetic variation exists in the protein expression profile of VENs, suggesting that humans might have evolved biochemical specializations for enhanced interoceptive sensitivity.
Topics: Activating Transcription Factor 3; Adult; Animals; Cell Count; Cerebral Cortex; Female; Hominidae; Humans; Hylobatidae; Imaging, Three-Dimensional; Immunohistochemistry; Male; Middle Aged; Neurokinin B; Neurons; Receptors, Interleukin-4; Social Behavior; Young Adult
PubMed: 21140465
DOI: 10.1002/ajhb.21135