scholarly journals With the Permission of Microtubules: An Updated Overview on Microtubule Function During Axon Pathfinding

2021 ◽  
Vol 14 ◽  
Author(s):  
Carlos Sánchez-Huertas ◽  
Eloísa Herrera
Keyword(s):  
Growth Cone ◽  
Intracellular Signaling ◽  
Expression Patterns ◽  
Brain Regions ◽  
Extracellular Proteins ◽  
Projection Neurons ◽  
Axon Pathfinding ◽  
Guidance Receptors ◽  
Spatio Temporal ◽  
Intracellular Cascades

During the establishment of neural circuitry axons often need to cover long distances to reach remote targets. The stereotyped navigation of these axons defines the connectivity between brain regions and cellular subtypes. This chemotrophic guidance process mostly relies on the spatio-temporal expression patterns of extracellular proteins and the selective expression of their receptors in projection neurons. Axon guidance is stimulated by guidance proteins and implemented by neuronal traction forces at the growth cones, which engage local cytoskeleton regulators and cell adhesion proteins. Different layers of guidance signaling regulation, such as the cleavage and processing of receptors, the expression of co-receptors and a wide variety of intracellular cascades downstream of receptors activation, have been progressively unveiled. Also, in the last decades, the regulation of microtubule (MT) assembly, stability and interactions with the submembranous actin network in the growth cone have emerged as crucial effector mechanisms in axon pathfinding. In this review, we will delve into the intracellular signaling cascades downstream of guidance receptors that converge on the MT cytoskeleton of the growing axon. In particular, we will focus on the microtubule-associated proteins (MAPs) network responsible of MT dynamics in the axon and growth cone. Complementarily, we will discuss new evidences that connect defects in MT scaffold proteins, MAPs or MT-based motors and axon misrouting during brain development.

scholarly journals Timing and localization of myasthenia gravis-related gene expression

2021 ◽  
Author(s):  
Dana L.E. Vergoossen ◽  
Arlin Keo ◽  
Ahmed Mahfouz ◽  
Maartje G. Huijbers
Keyword(s):  
Skeletal Muscle ◽  
Myasthenia Gravis ◽  
Expression Patterns ◽  
Cortical Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Related Protein ◽  
Temporal Expression ◽  
Comprehensive Overview ◽  
Spatio Temporal

AbstractMyasthenia gravis (MG) is an acquired autoimmune disorder caused by autoantibodies binding acetylcholine receptors (AChR), muscle-specific kinase (MuSK), agrin or low-density lipoprotein receptor-related protein 4 (Lrp4). These autoantibodies inhibit neuromuscular transmission by blocking the function of these proteins, and thereby cause fluctuating skeletal muscle weakness. Several reports suggest that these autoantibodies might also affect the central nervous system (CNS) in MG patients. A comprehensive overview of the timing and localization of the expression of MG-related antigens in other organs is currently lacking. To investigate the spatio-temporal expression of MG-related genes outside skeletal muscle, we used in silico tools to assess public expression databases. Acetylcholine esterase, nicotinic AChR α1 subunit, agrin, collagen Q, Dok7, Lrp4, MuSK and rapsyn were included as MG-related genes because of their well-known involvement in either congenital or autoimmune MG. We investigated expression of MG-related genes in 1) all human tissues using GTEx data, 2) specific brain regions, 3) neurodevelopmental stages, and 4) cell types using datasets from the Allen Institute for Brain Sciences. MG-related genes show heterogenous spatio-temporal expression patterns in the human body as well as in the CNS. For each of these genes several (new) tissues, brain areas and cortical cell types with (relatively) high expression were identified suggesting a potential role for these genes outside skeletal muscle. The possible presence of MG-related antigens outside skeletal muscle suggests that autoimmune MG, congenital MG or treatments targeting the same proteins may affect MG-related protein function in other organs.

The metalloproteinase ADAM10 is required for retinal ganglion cell axon guidance in the developing visual systems

2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Y. Y. Chen ◽  
C. L. Hehr ◽  
K. Atkinson-Leadbeater ◽  
J. C. Hocking ◽  
S. McFarlane
Keyword(s):  
Ganglion Cell ◽  
Axon Guidance ◽  
Retinal Ganglion Cell ◽  
Growth Cone ◽  
Expression Patterns ◽  
Optic Tract ◽  
Axon Growth ◽  
Proteolytic Processing ◽  
Retinal Ganglion

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis. Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10). Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease. References Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289(5483):1360-5. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123(2):291-304. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90(2):271-80.

scholarly journals Genome Wide Analysis of the Transcriptional Profiles in Different Regions of the Developing Rice Grains

Rice ◽  
2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ting-Ying Wu ◽  
Marlen Müller ◽  
Wilhelm Gruissem ◽  
Navreet K. Bhullar
Keyword(s):  
Gene Expression ◽  
Dna Sequence ◽  
Expression Patterns ◽  
Grain Filling ◽  
Aleurone Layer ◽  
Rice Grain ◽  
Sequence Motifs ◽  
Grain Development ◽  
Spatio Temporal ◽  
Dna Sequence Motifs

Abstract Background Rice is an important food source for humans worldwide. Because of its nutritional and agricultural significance, a number of studies addressed various aspects of rice grain development and grain filling. Nevertheless, the molecular processes underlying grain filling and development, and in particular the contributions of different grain tissues to these processes, are not understood. Main Text Using RNA-sequencing, we profiled gene expression activity in grain tissues comprised of cross cells (CC), the nucellar epidermis (NE), ovular vascular trace (OVT), endosperm (EN) and the aleurone layer (AL). These tissues were dissected using laser capture microdissection (LCM) at three distinct grain development stages. The mRNA expression datasets offer comprehensive and new insights into the gene expression patterns in different rice grain tissues and their contributions to grain development. Comparative analysis of the different tissues revealed their similar and/or unique functions, as well as the spatio-temporal regulation of common and tissue-specific genes. The expression patterns of genes encoding hormones and transporters indicate an important role of the OVT tissue in metabolite transport during grain development. Gene co-expression network prediction on OVT-specific genes identified several distinct and common development-specific transcription factors. Further analysis of enriched DNA sequence motifs proximal to OVT-specific genes revealed known and novel DNA sequence motifs relevant to rice grain development. Conclusion Together, the dataset of gene expression in rice grain tissues is a novel and useful resource for further work to dissect the molecular and metabolic processes during rice grain development.

scholarly journals Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

2008 ◽  
Vol 100 (4) ◽  
pp. 2015-2025 ◽  
Author(s):  
Julie E. Miller ◽  
Elizabeth Spiteri ◽  
Michael C. Condro ◽  
Ryan T. Dosumu-Johnson ◽  
Daniel H. Geschwind ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Vocal Learning ◽  
Brain Regions ◽  
Motor Deficits ◽  
Mrna Levels ◽  
Adult Males ◽  
Protein Levels ◽  
Area X

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex

2010 ◽  
Vol 41 (2) ◽  
pp. 146-160 ◽  
Author(s):  
Véronique Kemmel ◽  
Christian Klein ◽  
Doulaye Dembélé ◽  
Bernard Jost ◽  
Omar Taleb ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Expression Patterns ◽  
Cell Communication ◽  
Alcohol Withdrawal Syndrome ◽  
Brain Regions ◽  
Rat Hippocampus ◽  
Transport Systems ◽  
Cellular Mechanisms ◽  
Biological Regulation ◽  
Nucleotide Binding Sites

γ-Hydroxybutyrate (GHB) is a natural brain neuromodulator that has its own enzymatic machinery for synthesis and degradation, release, and transport systems and several receptors that belong to the G protein-coupled receptor (GPCR) family. Targeting of this system with exogenous GHB is used in therapy to induce sleep and anesthesia and to reduce alcohol withdrawal syndrome. GHB is also popular as a recreational drug for its anxiolytic and mild euphoric effects. However, in both cases, GHB must be administered at high doses in order to maintain GHB concentrations in brain of ∼800–1,000 μM. These high concentrations are thought to be necessary for interactions with low-affinity sites on GABAB receptor, but the molecular targets and cellular mechanisms modulated by GHB remain poorly characterized. Therefore, to provide new insights into the elucidation of GHB mechanisms of action and open new tracks for future investigations, we explored changes of GHB-induced transcriptomes in rat hippocampus and prefrontal cortex by using DNA microarray studies. We demonstrate that a single acute anesthetic dose of 1 g/kg GHB alters a large number of genes, 121 in hippocampus and 53 in prefrontal cortex; 16 genes were modified simultaneously in both brain regions. In terms of molecular functions, the majority of modified genes coded for proteins or nucleotide binding sites. In terms of Gene Ontology (GO) functional categories, the largest groups were involved in metabolic processing for hippocampal genes and in biological regulation for prefrontal cortex genes. The majority of genes modified in both structures were implicated in cell communication processes. Western blot and immunohistochemical studies carried out on eight selected proteins confirmed the microarray findings.

scholarly journals Uncovering the spatio-temporal dynamics of value-based decision-making in the human brain: a combined fMRI–EEG study

2014 ◽  
Vol 369 (1655) ◽  
pp. 20130473 ◽  
Author(s):  
Tobias Larsen ◽  
John P. O'Doherty
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Temporal Dynamics ◽  
Brain Regions ◽  
Choice Task ◽  
Binary Choice ◽  
Intraparietal Sulcus ◽  
Trial Onset ◽  
Eeg Data ◽  
Spatio Temporal

While there is a growing body of functional magnetic resonance imaging (fMRI) evidence implicating a corpus of brain regions in value-based decision-making in humans, the limited temporal resolution of fMRI cannot address the relative temporal precedence of different brain regions in decision-making. To address this question, we adopted a computational model-based approach to electroencephalography (EEG) data acquired during a simple binary choice task. fMRI data were also acquired from the same participants for source localization. Post-decision value signals emerged 200 ms post-stimulus in a predominantly posterior source in the vicinity of the intraparietal sulcus and posterior temporal lobe cortex, alongside a weaker anterior locus. The signal then shifted to a predominantly anterior locus 850 ms following the trial onset, localized to the ventromedial prefrontal cortex and lateral prefrontal cortex. Comparison signals between unchosen and chosen options emerged late in the trial at 1050 ms in dorsomedial prefrontal cortex, suggesting that such comparison signals may not be directly associated with the decision itself but rather may play a role in post-decision action selection. Taken together, these results provide us new insights into the temporal dynamics of decision-making in the brain, suggesting that for a simple binary choice task, decisions may be encoded predominantly in posterior areas such as intraparietal sulcus, before shifting anteriorly.

scholarly journals Single-cell transcriptomic analysis identifies neocortical developmental differences between human and mouse

2020 ◽  
Author(s):  
Ziheng Zhou ◽  
Shuguang Wang ◽  
Dengwei Zhang ◽  
Xiaosen Jiang ◽  
Jie Li ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Single Cell ◽  
Developmental Trajectories ◽  
Expression Patterns ◽  
Development Stage ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Cerebral Cortex Development ◽  
Excitatory Neurons ◽  
Human And Mouse

AbstractBackgroundThe specification and differentiation of neocortical projection neurons is a complex process under precise molecular regulation; however, little is known about the similarities and differences in cerebral cortex development between human and mouse at single-cell resolution.ResultsHere, using single-cell RNA-seq (scRNA-seq) data we explore the divergence and conservation of human and mouse cerebral cortex development using 18,446 and 7,610 neocortical cells. Systematic cross-species comparison reveals that the overall transcriptome profile in human cerebral cortex is similar to that in mouse such as cell types and their markers genes. By single-cell trajectories analysis we find human and mouse excitatory neurons have different developmental trajectories of neocortical projection neurons, ligand-receptor interactions and gene expression patterns. Further analysis reveals a refinement of neuron differentiation that occurred in human but not in mouse, suggesting that excitatory neurons in human undergo refined transcriptional states in later development stage. By contrast, for glial cells and inhibitory neurons we detected conserved developmental trajectories in human and mouse.ConclusionsTaken together, our study integrates scRNA-seq data of cerebral cortex development in human and mouse, and uncovers distinct developing models in neocortical projection neurons. The earlier activation of cognition -related genes in human may explain the differences in behavior, learning or memory abilities between the two species.

scholarly journals Cloning, Characterization, and Expression Features of Chicken CDS2 Splicing Variants

2020 ◽  
Author(s):  
Yuanyuan Xu ◽  
Shuping Zhang ◽  
Yujun Guo ◽  
Wen Chen ◽  
Yanqun Huang
Keyword(s):  
Adipose Tissue ◽  
Real Time ◽  
Real Time Pcr ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Exogenous Insulin ◽  
Quantitative Real Time Pcr ◽  
Temporal Expression ◽  
Spatio Temporal ◽  
The Brain

Abstract Background: The CDS gene encodes the CDP-diacylglycerol synthase enzyme that catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid. At present, there are no reports of CDS2 in birds. Here, we identified chicken CDS2 transcripts by combining conventional RT- PCR amplification, 5' RACE (Fig. 1A), and 3' RACE, explored the spatio-temporal expression profiles of total CDS2 and the longest transcript variant CDS2-4, and investigated the effect of exogenous insulin on total the mRNA level of CDS2 by quantitative real-time PCR. Results: Four transcripts of chicken CDS2 (CDS2-1, -2, -3, and -4) were identified, which were alternatively spliced at the 3′-untranslated region (UTR). CDS2 was widely expressed in all tissues examined and the longest variant CDS2-4 was the major transcript. Both total CDS2 and CDS2-4 were prominently expressed in adipose tissue and the heart, and exhibited low expression in the liver and pectoralis of 49 day-old chickens. Quantitative real-time PCR revealed that total CDS2 and CDS2-4 had different spatio-temporal expression patterns in chicken. Total CDS2 exhibited a similar temporal expression tendency with a high level in the later period of incubation (embryonic day 19 [E19] or 1-day-old) in the brain, liver, and pectoralis. While CDS2-4 presented a distinct temporal expression pattern in these tissues, CDS2-4 levels peaked at 21 days in the brain and pectoralis, while liver CDS2-4 mRNA levels were highest at the early stage of hatching (E10). Total CDS2 (P < 0.001) and CDS2-4 (P = 0.0090) mRNA levels in the liver were differentially regulated throughout development of the chicken. Exogenous insulin significantly downregulated the level of total CDS2 at 240 min in the pectoralis of Silky chickens (P < 0.01). Total CDS2 levels in the liver of Silky chickens were higher than that of the broiler in the basal state and after insulin stimulation. Conclusion: Chicken CDS2 has multiple transcripts with variation at the 3′-UTR, which was prominently expressed in adipose tissue. Total CDS2 and CDS2-4 presented distinct spatio-temporal expression patterns, and they were differentially regulated with age in liver. Insulin could regulate chicken CDS2 levels in a breed- and tissue-specific manner.

Functional equivalence of the transcription factors Pax2 and Pax5 in mouse development

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3703-3713 ◽  
Author(s):  
M. Bouchard ◽  
P. Pfeffer ◽  
M. Busslinger
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
Brain Regions ◽  
Vertebrate Evolution ◽  
Developmental Expression ◽  
Temporal Expression ◽  
Mouse Development ◽  
Highly Sensitive ◽  
Organizing Center ◽  
Cerebellum Development

Pax2 and Pax5 arose by gene duplication at the onset of vertebrate evolution and have since diverged in their developmental expression patterns. They are expressed in different organs of the mouse embryo except for their coexpression at the midbrain-hindbrain boundary (MHB), which functions as an organizing center to control midbrain and cerebellum development. During MHB development, Pax2 expression is initiated prior to Pax5 transcription, and Pax2(−/−) embryos fail to generate the posterior midbrain and cerebellum, whereas Pax5(−/−) mice exhibit only minor patterning defects in the same brain regions. To investigate whether these contrasting phenotypes are caused by differences in the temporal expression or biochemical activity of these two transcription factors, we have generated a knock-in (ki) mouse, which expresses a Pax5 minigene under the control of the Pax2 locus. Midbrain and cerebellum development was entirely rescued in Pax2(5ki/5ki) embryos. Pax5 could furthermore completely substitute for the Pax2 function during morphogenesis of the inner ear and genital tracts, despite the fact that the Pax5 transcript of the Pax2(5ki)allele was expressed only at a fivefold lower level than the wild-type Pax2 mRNA. As a consequence, the Pax2(5ki)allele was able to rescue most but not all Pax2 mutant defects in the developing eye and kidney, both of which are known to be highly sensitive to Pax2 protein dosage. Together these data demonstrate that the transcription factors Pax2 and Pax5 have maintained equivalent biochemical functions since their divergence early in vertebrate evolution.

Sign in / Sign up

Export Citation Format

Share Document