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Growth cone

Armando L Garcia, Adanna Udeh, Karthik Kalahasty, Abigail S Hackam
The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy...
January 2018: Neural Regeneration Research
Nicolas Unsain, Martin D Bordenave, Gaby F Martinez, Jalil Sami, Catalina von Bilderling, Federico M Barabas, Luciano A Masullo, Aaron D Johnstone, Philip A Barker, Bisbal Mariano, Fernando D Stefani, Alfredo O Cáceres
Axonal degeneration occurs in the developing nervous system for the appropriate establishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW). We found that F-actin decrease and growth cone collapse (GCC) occur early after TFW; however, treatments that prevent axonal fragmentation failed to prevent GCC, suggesting independent pathways...
February 14, 2018: Scientific Reports
R Suzuki, K Hotta, K Oka
The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMP mito ), and little is known about the dynamics of native mitochondrial ATP (ATP mito ). This study conducted simultaneous imaging of IMP mito and ATP mito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity...
February 14, 2018: Scientific Reports
Jung-Hyun Choi, Wei Wang, Dongkeun Park, Sung-Hoon Kim, Kyong-Tai Kim, Kyung-Tai Min
In neuronal development, dynamic rearrangement of actin promotes axonal growth cone extension, and spatiotemporal translation of local mRNAs in response to guidance cues directs axonal growth cone steering, where cofilin plays a critical role. While regulation of cofilin activity is well studied, regulatory mechanism for cofilin mRNA translation in neurons is unknown. In eukaryotic cells, proteins can be synthesized by cap-dependent or cap-independent mechanism via internal ribosome entry site (IRES)-mediated translation...
February 12, 2018: EMBO Journal
Andreea Belu, Mehmet Yilmaz, Elmar Neumann, Andreas Offenhäusser, Gokhan Demirel, Dirk Mayer
Three dimensional, nanostructured surfaces have attracted considerable attention in biomedical research since they have proven to represent a powerful platform to influence cell fate. In particular, nanorods and nanopillars possess great potential for the control of cell adhesion and differentiation, gene and biomolecule delivery, optical and electrical stimulation and recording, as well as cell patterning. Here, we investigate the influence of asymmetric poly(dichloro-p-xylene) (PPX) columnar films on the adhesion and maturation of cortical neurons...
February 10, 2018: Journal of Biomedical Materials Research. Part A
Yaxian Wang, Qianqian Shan, Jiacheng Pan, Sheng Yi
Actin cytoskeleton regulates many essential biological functions, including cellular development, shape, polarity, and motility. The organization of actin cytoskeleton has also been associated with numerous physiological and pathological conditions, for instance, the elongation of axonal growth cone during peripheral nerve regeneration. However, the spatio-temporal expression patterns of actin cytoskeleton-related genes and the specific roles of actin cytoskeleton following peripheral nerve injury have not been fully revealed...
2018: Frontiers in Physiology
Pei-Pei Meng, Zhe Li, Sheng-Yu Wang, Wen-Wen Zhou, Malik Samiullah, Na Chen, Fang-Hong Luo, Ting Wu, Jiang-Hua Yan
Class three semaphorins were originally identified as mediators of axon guidance, which repelled axons and collapsed growth cones. As a member of class three semaphorins, semaphorin3F (Sema3F) has been found to have similar effects on tumor cells and endothelial cells and also is implicated in the signaling of tumor metastasis by forming a complex with neuropilins and plexins. In this study, our laboratory produced a monoclonal antibody against the C-terminal domain of Sema3F (Sema3Fc mAb) using the hybridoma method, expecting to explore the potential role of the antibody and its application in the detection of Sema3F...
February 8, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Tong Wu, Jiajia Xue, Haoxuan Li, Chunlei Zhu, Xiumei Mo, Younan Xia
Scaffolds functionalized with circular gradients of active proteins are attractive for tissue regeneration due to their enhanced capability to accelerate cell migration and/or promote neurite extension in a radial fashion. Here we report a general method for generating circular gradients of active proteins on scaffolds comprised of radially aligned nanofibers. In a typical process, the scaffold, with its central portion raised using a copper wire to take a cone shape, was placed in a container (upright or up-side-down), followed by dropwise addition of a bovine serum albumin (BSA) solution into the container...
February 8, 2018: ACS Applied Materials & Interfaces
Eun-Ju Jin, Hyo Rim Ko, Inwoo Hwang, Byeong-Seong Kim, Jeong-Yun Choi, Kye Won Park, Sung-Woo Cho, Jee-Yin Ahn
Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved threonine residue and modulate neurite outgrowth. Here we show that Akt binds to and phosphorylates a threonine 573 residue on radixin. Akt-mediated phosphorylation protects radixin from ubiquitin-dependent proteasomal degradation, thereby enhancing radixin protein stability, which permits proper neurite outgrowth and growth cone formation...
February 7, 2018: Scientific Reports
Xin Xin Xiong, Feng Pan, Ruo Qiao Chen, Dian Xing Hu, Xin Yao Qiu, Chun Yang Li, Xiao Qiang Xie, Bo Tian, Xiao Qian Chen
Cerebral ischemia causes severe cell death or injury including axon breakdown or retraction in the brain. Axon regeneration is crucial for the functional recovery of injured neurons or brains after ischemia/reperfusion (I/R); however, this process has been proved extremely difficult in adult brains and there is still no effective therapy for it. Here we reported that neuroglobin (Ngb), a novel oxygen-binding or sensor protein existing predominantly in neurons or brains, functions as a driving factor for axon regeneration during I/R...
February 7, 2018: Cell Death & Disease
Kathryn A Schiel
This etiologic model proposes that Alzheimers Disease (AD) arises when an unusually rapid increase in ventricle volume triggers axon stretch that culminates in the physical separation of trans-synaptic proteins. As a result, these proteins, such as neurexin, neuroligin, N-Cadherin and Amyloid Precursor Protein (APP), experience a change in the configuration of their cytoplasmic tail, so that instead of transmitting signals to create and maintain synaptic structure they activate enzymes, and generate molecules, that stimulate neurite growth; for example, the transformation of the N-Cadherin tail dissolves its complex with presenilin and β-catenin triggering activation of glycogen synthase kinase 3 beta (GSK3β) and cytoskeletal disruption...
February 2018: Medical Hypotheses
Shuang Gao, Gang Liu, Qilai Chen, Wuhong Xue, Huali Yang, Jie Shang, Bin Chen, Fei Zeng, Cheng Song, Feng Pan, Run-Wei Li
Resistive random access memory (RRAM) with inherent logic-in-memory capability exhibits great potential to construct beyond von-Neumann computers. Particularly, unipolar RRAM is more promising because its single polarity operation enables large-scale crossbar logic-in-memory circuits with the highest integration density and simpler peripheral control circuits. However, unipolar RRAM usually exhibits poor switching uniformity due to random activation of conducting filaments and consequently cannot meet the strict uniformity requirement for logic-in-memory application...
February 1, 2018: ACS Applied Materials & Interfaces
Huai Huang, Tao Yang, Qiangqiang Shao, Tanushree Majumder, Kristopher Mell, Guofa Liu
Heterozygous missense mutations in human TUBB3 gene result in a spectrum of brain malformations associated with defects in axon guidance, neuronal migration and differentiation. However, the molecular mechanisms underlying mutation-related axon guidance abnormalities are unclear. Recent studies have shown that netrin-1, a canonical guidance cue, induced the interaction of TUBB3 with the netrin receptor deleted in colorectal cancer (DCC). Furthermore, TUBB3 is required for netrin-1-induced axon outgrowth, branching and pathfinding...
January 27, 2018: Neuroscience
Matthias Schlau, Daniel Terheyden-Keighley, Verena Theis, Hans Georg Mannherz, Carsten Theiss
A crucial neuronal structure for the development and regeneration of neuronal networks is the axonal growth cone. Affected by different guidance cues, it grows in a predetermined direction to reach its final destination. One of those cues is the vascular endothelial growth factor (VEGF), which was identified as a positive effector for growth cone movement. These positive effects are mainly mediated by a reorganization of the actin network. This study shows that VEGF triggers a tight colocalization of cofilin and the Arp2/3 complex to the actin cytoskeleton within chicken dorsal root ganglia (DRG)...
January 27, 2018: International Journal of Molecular Sciences
T Sallstedt, S Bengtson, C Broman, P M Crill, D E Canfield
Fossil microbiotas are rare in the early rock record, limiting the type of ecological information extractable from ancient microbialites. In the absence of body fossils, emphasis may instead be given to microbially derived features, such as microbialite growth patterns, microbial mat morphologies, and the presence of fossilized gas bubbles in lithified mats. The metabolic affinity of micro-organisms associated with phosphatization may reveal important clues to the nature and accretion of apatite-rich microbialites...
January 30, 2018: Geobiology
Eszter N Tóth, Akshar Lohith, Manas Mondal, Jia Guo, Akiyoshi Fukamizu, Nader Pourmand
In highly polarized cells such as neurons, compartmentalization of mRNA and of local protein synthesis enables remarkably fast, precise, and local responses to external stimuli. These responses are highly important for neuron growth cone guidance, synapse formation, and regeneration following injury. Because an altered spatial distribution of mRNA can result in mental retardation or neurodegenerative diseases, subcellular transcriptome analysis of neurons could be a useful tool for studying these conditions, but current techniques, such as in situ hybridization, bulk microarray, or RNA-Seq, impose tradeoffs between spatial resolution and multiplexing...
January 29, 2018: Journal of Biological Chemistry
Min Zhang, Qiang Zhou, Yuncin Luo, Tara Nguyen, Mark I Rosenblatt, Victor H Guaiquil
The peripheral sensory nerves that innervate the cornea can be easily damaged by trauma, surgery, infection or diabetes. Several growth factors and axon guidance molecules, such as Semaphorin3A (Sema3A) are upregulated upon cornea injury. Nerves can regenerate after injury but do not recover their original density and patterning. Sema3A is a well known axon guidance and growth cone repellent protein during development, however its role in adult cornea nerve regeneration remains undetermined. Here we investigated the neuro-regenerative potential of Sema3A on adult peripheral nervous system neurons such as those that innervate the cornea...
2018: PloS One
Yuan Ren, Michael J Mlodzianoski, Aih Cheun Lee, Fang Huang, Daniel Marcel Suter
<i>Objective</i>. Current neuronal cell culture is mostly performed on two-dimensional (2D) surfaces, which lack many of the important features of the native environment of neurons, including topographical cues, deformable extracellular matrix, and spatial isotropy or anisotropy in three dimensions. Although three-dimensional (3D) cell culture systems provide a more physiologically relevant environment than 2D systems, their popularity is greatly hampered by the lack of easy-to-make and -use devices...
January 24, 2018: Journal of Neural Engineering
Chih-Ju Chang, Ming-Yuan Chang, Szu-Yi Chou, Chi-Chen Huang, Jian-Ying Chuang, Tsung-I Hsu, Hsing-Fang Chang, Yi-Hsin Wu, Chung-Che Wu, Daniel Morales, Artur Kania, Tzu-Jen Kao
The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb...
January 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sergio Astigarraga, Jessica Douthit, Dorota Tarnogorska, Matthew S Creamer, Omer Mano, Damon A Clark, Ian A Meinertzhagen, Jessica E Treisman
The assembly of functional neuronal circuits requires growth cones to extend in defined directions and recognize the correct synaptic partners. Homophilic adhesion between vertebrate Sidekick proteins promotes synapse formation between retinal neurons involved in visual motion detection. We show here that Drosophila Sidekick accumulates in specific synaptic layers of the developing motion detection circuit and is necessary for normal optomotor behavior. Sidekick is required in photoreceptors, but not in their target lamina neurons, to promote the alignment of lamina neurons into columns and subsequent sorting of photoreceptor axons into synaptic modules based on their precise spatial orientation...
February 5, 2018: Development
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