scholarly journals Drosophila Stathmin: A Microtubule-destabilizing Factor Involved in Nervous System Formation

2002 ◽  
Vol 13 (2) ◽  
pp. 698-710 ◽  
Author(s):  
Sylvie Ozon ◽  
Antoine Guichet ◽  
Olivier Gavet ◽  
Siegfried Roth ◽  
André Sobel
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Microtubule Assembly ◽  
Nervous Systems ◽  
Germ Cell Migration ◽  
Numerous Cell ◽  
First Time

Stathmin is a ubiquitous regulatory phosphoprotein, the generic element of a family of neural phosphoproteins in vertebrates that possess the capacity to bind tubulin and interfere with microtubule dynamics. Although stathmin and the other proteins of the family have been associated with numerous cell regulations, their biological roles remain elusive, as in particular inactivation of the stathmin gene in the mouse resulted in no clear deleterious phenotype. We identified stathmin phosphoproteins inDrosophila, encoded by a unique gene sharing the intron/exon structure of the vertebrate stathmin andstathmin family genes. They interfere with microtubule assembly in vitro, and in vivo when expressed in HeLa cells. Drosophila stathmin expression is regulated during embryogenesis: it is high in the migrating germ cells and in the central and peripheral nervous systems, a pattern resembling that of mammalian stathmin. Furthermore, RNA interference inactivation ofDrosophila stathmin expression resulted in germ cell migration arrest at stage 14. It also induced important anomalies in nervous system development, such as loss of commissures and longitudinal connectives in the ventral cord, or abnormal chordotonal neuron organization. In conclusion, a single Drosophilagene encodes phosphoproteins homologous to the entire vertebrate stathmin family. We demonstrate for the first time their direct involvement in major biological processes such as development of the reproductive and nervous systems.

scholarly journals Regulation of miRNAs during Retinoic Acid-Induced Regeneration of a Molluscan Central Nervous System

2018 ◽  
Author(s):  
Sarah E. Walker ◽  
Gaynor E. Spencer ◽  
Alexsandr Necakov ◽  
Robert L. Carlone
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Lymnaea Stagnalis ◽  
System Development ◽  
Growth Cones ◽  
Nervous System Development ◽  
Biologically Active ◽  
Neuronal Outgrowth ◽  
First Time

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

scholarly journals CD60b: Enriching Neural Stem/Progenitor Cells from Rat Development into Adulthood

2017 ◽  
Vol 2017 ◽  
pp. 1-16
Author(s):  
Fernanda Gubert ◽  
Camila Zaverucha-do-Valle ◽  
Michelle Furtado ◽  
Pedro M. Pimentel-Coelho ◽  
Nicoli Mortari ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Neurogenic Niche ◽  
Neural Stem Progenitor Cells

CD60b antigens are highly expressed during development in the rat nervous system, while in the adult their expression is restricted to a few regions, including the subventricular zone (SVZ) around the lateral ventricles—a neurogenic niche in the adult brain. For this reason, we investigated whether the expression of C60b is associated with neural stem/progenitor cells in the SVZ, from development into adulthood. We performedin vitroandin vivoanalyses of CD60b expression at different stages and identified the presence of these antigens in neural stem/progenitor cells. We also observed that CD60b could be used to purify and enrich a population of neurosphere-forming cells from the developing and adult brain. We showed that CD60b antigens (mainly corresponding to ganglioside 9-O-acetyl GD3, a well-known molecule expressed during central nervous system development and mainly associated with neuronal migration) are also present in less mature cells and could be used to identify and isolate neural stem/progenitor cells during development and in the adult brain. A better understanding of molecules associated with neurogenesis may contribute not only to improve the knowledge about the physiology of the mammalian central nervous system, but also to find new treatments for regenerating tissue after disease or brain injury.

scholarly journals Laminar specific attachment and neurite outgrowth of thalamic neurons on cultured slices of developing cerebral neocortex

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2811-2822 ◽  
Author(s):  
D.E. Emerling ◽  
A.D. Lander
Keyword(s):  
Cell Attachment ◽  
System Development ◽  
Nervous System Development ◽  
Cortical Plate ◽  
Spatial Patterning ◽  
Extracellular Matrix Molecules ◽  
Process Outgrowth ◽  
Cultured Slices

In nervous system development, the growth cones of advancing axons are thought to navigate to their targets by recognizing cell-surface and extracellular matrix molecules that act as specific guidance cues. To identify and map cues that guide the growth of a particular axonal system, the thalamocortical afferents, an assay was devised to examine short-term interactions of dissociated embryonic thalamic cells with living, approximately 150 microns slices of developing mouse forebrain. Thalamic cells rapidly (< 3 hours) and efficiently attached to and extended neurites on pre- and postnatal slices, but a broad zone throughout the neocortex was generally non-permissive for both thalamic cell attachment and the ingrowth of neurites. This zone coincided with the cortical plate at early stages (embryonic day 15), but later became restricted, in rostral-to-caudal fashion, to cortical laminae 2/3. Thus, at each stage, thalamic cells in vitro avoided just that area that thalamic axons confront, but generally do not enter, in vivo. In addition, neurites that extended on some layers were found to be significantly oriented in directions that coincide with the pathways that thalamic axons follow in vivo. These results imply that local adhesive cues and signals that affect process outgrowth are distributed among developing cortical laminae in a manner that could underlie much of the temporal and spatial patterning of thalamocortical innervation.

scholarly journals Modeling Brain Somatic Mosaicism With Cerebral Organoids, Including a Note on Mutant Microglia

2019 ◽  
Vol 12 ◽  
Author(s):  
Bert M. Verheijen
Keyword(s):  
Nervous System ◽  
System Development ◽  
Somatic Mosaicism ◽  
3D Culture ◽  
3D Cell Culture ◽  
Nervous System Development ◽  
Genomic Diversity ◽  
Human Organ ◽  
Development And Aging

The brain is a genomic mosaic. Cell-to-cell genomic differences, which are the result of somatic mutations during development and aging, contribute to cellular diversity in the nervous system. This genomic diversity has important implications for nervous system development, function, and disease. Brain somatic mosaicism might contribute to individualized behavioral phenotypes and has been associated with several neuropsychiatric and neurodegenerative disorders. Therefore, understanding the causes and consequences of somatic mosaicism in neural circuits is of great interest. Recent advances in 3D cell culture technology have provided new means to study human organ development and various human pathologies in vitro. Cerebral organoids (“mini-brains”) are pluripotent stem cell-derived 3D culture systems that recapitulate, to some extent, the developmental processes and organization of the developing human brain. Here, I discuss the application of these neural organoids for modeling brain somatic mosaicism in a lab dish. Special emphasis is given to the potential role of microglial mutations in the pathogenesis of neurodegenerative diseases.

Integrin alpha 6 expression is required for early nervous system development in Xenopus laevis

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2539-2554 ◽  
Author(s):  
T.E. Lallier ◽  
C.A. Whittaker ◽  
D.W. DeSimone
Keyword(s):  
Nervous System ◽  
Early Development ◽  
System Development ◽  
Cranial Nerves ◽  
Nervous System Development ◽  
Neural Plate ◽  
Pronephric Duct ◽  
Axial Defects ◽  
Integrin Alpha 6

The integrin alpha 6 subunit pairs with both the beta 1 and beta 4 subunits to form a subfamily of laminin receptors. Here we report the cDNA cloning and primary sequence for the Xenopus homologue of the mammalian integrin alpha 6 subunit. We present data demonstrating the spatial and temporal expression of alpha 6 mRNA and protein during early development. Initially, alpha 6 transcripts are expressed in the dorsal ectoderm and future neural plate at the end of gastrulation. Later in development, alpha 6 mRNAs are expressed in a variety of neural derivatives, including the developing sensory placodes (otic and olfactory) and commissural neurons within the neural tube. Integrin alpha 6 is also expressed in the elongating pronephric duct as well as a subset of the rhombencephalic neural crest, which will form the Schwann cells lining several cranial nerves (VII, VIII and X). In vivo expression of an alpha 6 antisense transcript in the animal hemisphere leads to a reduction in alpha 6 protein expression, a loss of adhesion to laminin, and severe defects in normal development. In 35% of cases, reduced levels of alpha 6 expression result in embryos that complete gastrulation normally but arrest at neurulation prior to the formation of the neural plate. In an additional 22% of cases, embryos develop with severe axial defects, including complete loss of head or tail structures. In contrast, overexpression of the alpha 6 subunit by injection of full-length mRNA has no apparent effect on embryonic development. Co-injection of antisense and sense plasmid constructs results in a partial rescue of the antisense-generated phenotypes. These data indicate that the integrin alpha 6 subunit is critical for the early development of the nervous system in amphibians.

Neurons from stem cells: Implications for understanding nervous system development and repair

2000 ◽  
Vol 78 (5) ◽  
pp. 613-628 ◽  
Author(s):  
Fiona C Mansergh ◽  
Michael A Wride ◽  
Derrick E Rancourt
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Differentiation ◽  
System Development ◽  
Nervous System Development ◽  
Neural Cells ◽  
Ageing Population ◽  
Bioinformatic Tools ◽  
Functional Characterisation

Neurodegenerative diseases cost the economies of the developed world billions of dollars per annum. Given ageing population profiles and the increasing extent of this problem, there has been a surge of interest in neural stem cells and in neural differentiation protocols that yield neural cells for therapeutic transplantation. Due to the oncogenic potential of stem cells a better characterisation of neural differentiation, including the identification of new neurotrophic factors, is required. Stem cell cultures undergoing synchronous in vitro neural differentiation provide a valuable resource for gene discovery. Novel tools such as microarrays promise to yield information regarding gene expression in stem cells. With the completion of the yeast, C. elegans, Drosophila, human, and mouse genome projects, the functional characterisation of genes using genetic and bioinformatic tools will aid in the identification of important regulators of neural differentiation.Key words: neural differentiation, neural precursor cell, brain repair, central nervous system repair, CNS.

scholarly journals Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo

2006 ◽  
Vol 11 (5) ◽  
pp. 054022 ◽  
Author(s):  
Szu-Yu Chen ◽  
Cho-Shuen Hsieh ◽  
Shi-Wei Chu ◽  
Cheng-Yung Lin ◽  
Ching-Yi Ko ◽  
...  
Keyword(s):  
Nervous System ◽  
Optical Microscopy ◽  
System Development ◽  
Nervous System Development ◽  
Embryonic Nervous System ◽  
Long Term Observation

scholarly journals Different Subcellular Localization of ALCAM Molecules in Neuroblastoma: Association with Relapse

2010 ◽  
Vol 32 (1-2) ◽  
pp. 77-86
Author(s):  
Maria Valeria Corrias ◽  
Claudio Gambini ◽  
Andrea Gregorio ◽  
Michela Croce ◽  
Gaia Barisione ◽  
...  
Keyword(s):  
Nervous System ◽  
Subcellular Localization ◽  
Cell Lines ◽  
System Development ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Nervous System Development ◽  
Primary Tumors ◽  
Neuroblastoma Cell Lines

Background: The Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD), involved in nervous system development, has been linked to tumor progression and metastasis in several tumors. No information is available on ALCAM expression in neuroblastoma, a childhood neoplasia originating from the sympathetic nervous system.Methods: ALCAM expression was analysed by immunofluorescence and immunohistochemistry on differentiated neuroblastoma cell lines and on archival specimens of stroma-poor, not MYCN amplified, resectable neuroblastoma tumors, respectively.Results: ALCAM is variously expressed in neuroblastoma cell lines, is shed by metalloproteases and is cleaved by ADAM17/TACE in vitro. ALCAM is expressed in neuroblastoma primary tumors with diverse patterns of subcellular localization and is highly expressed in the neuropil area in a subgroup of cases. Tumor specimens showing high expression of ALCAM at the membrane of the neuroblast body or low levels in the neuropil area are associated with relapse (P = 0.044 and P < 0.0001, respectively). In vitro differentiated neuroblastoma cells show strong ALCAM expression on neurites, suggesting that ALCAM expression in the neuropil is related to a differentiated phenotype.Conclusions: Assessment of ALCAM localization by immunohistochemistry may help to identify patients who, in the absence of negative prognostic factors, are at risk of relapse and require a more careful follow-up.

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