scholarly journals Chicken Acidic Leucine-rich EGF-like Domain Containing Brain Protein (CALEB), a Neural Member of the EGF Family of Differentiation Factors, Is Implicated in Neurite Formation

1997 ◽  
Vol 136 (4) ◽  
pp. 895-906 ◽  
Author(s):  
Stefan Schumacher ◽  
Hansjürgen Volkmer ◽  
Fritz Buck ◽  
Albrecht Otto ◽  
Attila Tárnok ◽  
...  
Keyword(s):  
Nervous System ◽  
Brain Protein ◽  
Binding Assays ◽  
Multidomain Protein ◽  
Differentiation Factors ◽  
Neurite Formation ◽  
Embryonic Nervous System ◽  
Egf Family ◽  
Developing Nervous System

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline–rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.

Developmental programmes of growth and survival in early sensory neurons

1991 ◽  
Vol 331 (1261) ◽  
pp. 259-262
Keyword(s):  
Nervous System ◽  
Sensory Neurons ◽  
Neurotrophic Factor ◽  
Target Distance ◽  
Trophic Factor ◽  
Growth And Survival ◽  
Target Field ◽  
Developing Nervous System

In the developing vertebrate nervous system the survival of neurons becomes dependent on the supply of a neurotrophic factor from their targets when their axons reach these targets. To determine how the onset of neurotrophic factor dependency is coordinated with the arrival of axons in the target field, we have studied the growth and survival of four populations of cranial sensory neurons whose axons have markedly different distances to grow to reach their targets. Axonal growth rate both in vivo and in vitro is related to target distance; neurons with more distant targets grow faster. The onset trophic factor dependency in culture is also related to target distance; neurons with more distant targets survive longer before becoming trophic factor dependent. These data suggest that programmes of growth and survival in early neurons play an important role in coordinating the timing of trophic interactions in the developing nervous system.

scholarly journals Establishment of an in vitro screening model of bioactive compounds from Vietnamese medicinal plants using the recombinant central nervous system receptors

2018 ◽  
Vol 34 (1) ◽  
Author(s):  
Pham Thi Hong Nhung ◽  
Dinh Doan Long
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Semliki Forest Virus ◽  
Viet Nam ◽  
In Vitro Screening ◽  
Binding Assays ◽  
Neurokinin 1 Receptor ◽  
Screening Model ◽  
Neurokinin 1

The central nervous system receptors are important targets of the drugs, involved in many neurological diseases. Therefore, this study was designed to build an in vitro screening model using recombinant receptors distributed in the central nervous system (CNS). Method: construction of cDNA system encoding for receptors; using Semliki Forest virus for the rapid and high expression of receptors in mammalian cell lines; designing binding assays for in vitro pharmacological studies of compounds and methanol plant extracts. Results: 24 cDNAs encoding for receptors and 1 screening kit with neurokinin-1 receptor were constructed; 4 receptors were expressed successfully. Conclusion: The in vitro screening model was established successfully and applied for NK1 receptors with high sensitivity and specificity. This model is a useful tool for discovery and development of target compounds acting in the CNS.   Keywords Recombinant CNS receptors, an in vitro screening assays, bioactive compounds, Semliki Forest virus. specificity References [1] Đỗ Huy Bích và cs, Cây thuốc và động vật làm thuốc ở Việt Nam, NXB Khoa học và kỹ thuật, 2004[2] Kenneth H. Lundstrom, M.L. Chiu, G Protein - Coupled receptors in Drug Discovery, Taylor & Francis Group, 2006[3] Zhu M., Bowery N.G., Greengrass P.M., Phillipson J.D., Application of radioligand receptor binding assays in the search for CNS active principles from Chinese medicinal plants, J. Ethnopharmacol. 54 (1996) 153[4] Phạm Thị Hồng Nhung, Hoàng Thị Mỹ Nhung, Đinh Đoàn Long, Cải biến vectơ hệ Virus Semliki Forest (SFV) nhằm biểu hiện thụ thể GPCR của người Việt Nam, Tạp chí Khoa học ĐHQGHN: Khoa học Tự nhiên và Công nghệ 31 (2015) 47[5] Berglund P., Sjoberg M., Garoff H., Atkins G.J., Sheahan B.J., and Liljestrom P., Semliki Forest virus expression system: production of conditionally infectious recombinant particles, Biotechnology 11 (1993) 916[6] Dinh DL, Pham THN, Hoang TMN, Trinh TC, Vo TTL, Pham TH, Kenneth L., Interaction of Vietnamese medicinal plant extracts with recombinantly expressed human neurokinin-1 receptor, Planta Medica Letters, 2(2015)42 [7] Rosso M., Mu᷈ Noz M., Berger M., The Role of Neurokinin -1 Receptor in the Microenvironment of Inflammation and Cancer, The Scientific World Journal, 2012 (2012)1[8] Tô Việt Bắc, Bùi Minh Đức, Phạm Thị Kim, Thử nghiệm khả năng gây độc trên chuột của chế phẩm rotundin, Tạp chí Y hoc Việt Nam, 7(1994)46[9] Violin J.D., Crombie A.L., Soergel D.G., Lark M.W., Biased ligands at G-protein-coupled receptors: promise and progress, Trends Pharmacol Sci, 35(2014) 308[10] Lundstrom K., Henningsen R., Semliki Forest virus vectors applied to receptor expression in cell lines and primary neurons, J. Neurochem 71 (1998) [11] Federal Register 58 No. 19, Addition of Appendix DL-X to the NIH guidelines regarding Semliki Forest virus. Human Gene Therapy. 1993. p.5.

scholarly journals A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination

1998 ◽  
Vol 140 (6) ◽  
pp. 1497-1509 ◽  
Author(s):  
Ruth S. Slack ◽  
Hiba El-Bizri ◽  
Josée Wong ◽  
Daniel J. Belliveau ◽  
Freda D. Miller
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Cortical Neurons ◽  
Adenovirus E1a ◽  
Neuronal Gene ◽  
Developing Neocortex ◽  
Postmitotic Neurons ◽  
Developing Nervous System

In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing neocortex. To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb−/− mice with transgenic mice expressing β-galactosidase from the early, panneuronal Tα1 α-tubulin promoter (Tα1:nlacZ). In E12.5 Rb−/− embryos, the Tα1:nlacZ transgene was robustly expressed throughout the developing nervous system. However, by E14.5, there were perturbations in Tα1:nlacZ expression throughout the nervous system, including deficits in the forebrain and retina. To more precisely define the temporal requirement for pRb in neuronal determination, we functionally ablated the pRb family in wild-type cortical progenitor cells that undergo the transition to postmitotic neurons in vitro by expression of a mutant adenovirus E1A protein. These studies revealed that induction of Tα1:nlacZ did not require proteins of the pRb family. However, in their absence, determined, Tα1:nlacZ-positive cortical neurons underwent apoptosis, presumably as a consequence of “mixed signals” deriving from their inability to undergo terminal mitosis. In contrast, when the pRb family was ablated in postmitotic cortical neurons, there was no effect on neuronal survival, nor did it cause the postmitotic neurons to reenter the cell cycle. Together, these studies define a critical temporal window of requirement for the pRb family; these proteins are not required for induction of neuronal gene expression or for the maintenance of postmitotic neurons, but are essential for determined neurons to exit the cell cycle and survive.

Oligodendrocyte precursor (O-2A progenitor cell) migration; a model system for the study of cell migration in the developing central nervous system

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 219-225 ◽  
Author(s):  
B. W. Kiernan ◽  
Charles ffrench-Constant
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Large Numbers ◽  
Multicellular Organisms ◽  
Developing Nervous System

Cell migration plays an important role in the development of complex multicellular organisms. The molecular mechanisms that regulate this migration arc therefore of great interest. Unfortunately, however, analysis of cell migration in vertebrates is hampered by the inaccessability of the cells and the difficulty of manipulating their environment within the embryo. This review focusses on one particular migratory cell population, the oligodendrocyte p1ecursor cell or O-2A progenitor cell, that gives rise to the myelin-forming oligodendrocytes within the CNS. These cells mi grate extensively during normal development. They can be purified and grown in large numbers in cell culture, so allowing the use of reductionist approaches using cell and molecular biology techniques. Moreover, cultured cells will migrate within the CNS following transplantation. As a result, the migration of these cells in vivo can be analysed following manipulation in vitro. Taken together, we believe that the different properties of these cells makes them excellent candidates for studies addressing the control of cell migration in the developing nervous system.

scholarly journals Identification of MoKA, a Novel F-Box Protein That Modulates Krüppel-Like Transcription Factor 7 Activity

2004 ◽  
Vol 24 (3) ◽  
pp. 1058-1069 ◽  
Author(s):  
Silvia Smaldone ◽  
Friedrich Laub ◽  
Cindy Else ◽  
Cecilia Dragomir ◽  
Francesco Ramirez
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Transcription Factor ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Direct Interaction ◽  
Proximal Promoter ◽  
F Box Protein ◽  
Developing Nervous System

ABSTRACT KLF7, a member of the Krüppel-like transcription factor family, is believed to regulate neurogenesis and cell cycle progression. Here, a yeast two-hybrid screen for KLF7 cofactors in the developing nervous system identified a novel 140-kDa protein named MoKA, for modulator of KLF7 activity. Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator, and in situ hybridizations identified the developing nervous system and the adult testes as two sites of MoKA and Klf7 coexpression. Chromatin immunoprecipitation experiments demonstrated KLF7 binding to the p21WAF1/Cip1 gene while transient transfection assays documented KLF7 stimulation of the p21WAF1/Cip1 proximal promoter. Additional tests revealed that distinct structural motifs of MoKA direct interaction with KLF7 and shuttling between the nucleus and cytoplasm of asynchronously cycling cells. Altogether, our results strongly suggest that MoKA and KLF7 interact functionally to regulate gene expression during cell differentiation and identify the cell cycle regulator p21WAF1/Cip1 as one of the targeted genes.

scholarly journals Dissection of Complex Molecular Interactions of Neurofascin with Axonin-1, F11, and Tenascin-R, Which Promote Attachment and Neurite Formation of Tectal Cells

1998 ◽  
Vol 142 (4) ◽  
pp. 1083-1093 ◽  
Author(s):  
Hansjürgen Volkmer ◽  
Ute Zacharias ◽  
Ursel Nörenberg ◽  
Fritz G. Rathjen
Keyword(s):  
Alternative Splicing ◽  
Neurite Outgrowth ◽  
Molecular Interactions ◽  
Cell Attachment ◽  
Binding Assays ◽  
Ig Superfamily ◽  
Competition Binding ◽  
Neurite Formation ◽  
Additional Protein

Neurofascin is a member of the L1 subgroup of the Ig superfamily that promotes axon outgrowth by interactions with neuronal NgCAM-related cell adhesion molecule (NrCAM). We used a combination of cellular binding assays and neurite outgrowth experiments to investigate mechanisms that might modulate the interactions of neurofascin. In addition to NrCAM, we here demonstrate that neurofascin also binds to the extracellular matrix glycoprotein tenascin-R (TN-R) and to the Ig superfamily members axonin-1 and F11. Isoforms of neurofascin that are generated by alternative splicing show different preferences in ligand binding. While interactions of neurofascin with F11 are only slightly modulated, binding to axonin-1 and TN-R is strongly regulated by alternatively spliced stretches located in the NH2-terminal half, and by the proline-alanine-threonine-rich segment. In vitro neurite outgrowth and cell attachment assays on a neurofascin-Fc substrate reveal a shift of cellular receptor usage from NrCAM to axonin-1, F11, and at least one additional protein in the presence of TN-R, presumably due to competition of the neurofascin– NrCAM interaction. Thereby, F11 binds to TN-R of the neurofascin/TN-R complex, but not to neurofascin, whereas axonin-1 is not able to bind directly to the neurofascin/TN-R complex as shown by competition binding assays. In conclusion, these investigations indicate that the molecular interactions of neurofascin are regulated at different levels, including alternative splicing and by the presence of interacting proteins.

A HISTOCHEMICAL AND BIOCHEMICAL STUDY OF THE POLYSACCHARIDIC SUBSTANCES OF THE DEVELOPING NERVOUS SYSTEM OF THE RAT IN RELATION WITH THE APPEARANCE OF CHOLINESTERASE ACTIVITY

1958 ◽  
Vol 36 (1) ◽  
pp. 275-288 ◽  
Author(s):  
Marc Crevier
Keyword(s):  
Nervous System ◽  
Acid Hydrolysis ◽  
Biochemical Study ◽  
Chemical Fractionation ◽  
High Concentration ◽  
Brain Substance ◽  
Pas Reaction ◽  
Irregular Action ◽  
Developing Nervous System

The PAS reaction and the cholinesterase reaction run parallel in the lower centers of the developing nervous system in the rat. Also, the two reactions appear progressively between the 10th and 15th day as the result of a chemical maturation of the neurons. Extraction of sections with methanol–chloroform does not alter the PAS reaction while acetylation inhibits it reversibly. These two facts suggest that 1,2-glycol groups are detected. Inhibition by hyaluronidase increases this evidence, despite the fact that diastase has a slight and irregular action. To elucidate the nature of the PAS reaction further, chemical fractionation of the brain substance has been attempted. (A) A fraction soluble in methanol–chloroform is metachromatic and PAS-positive in vitro. (B) A fraction soluble in a potassium chloride – potassium carbonate mixture is non-dialyzable, non-metachromatic, but PAS-positive. After acid hydrolysis it yields glucose but no hexosamine. (C) A fraction extracted from the residue by sodium hydroxide is non-dialyzable, non-metachromatic, but also PAS-positive. By chromatography and electrophoresis it is found to contain a non-sulphated mucoprotein yielding hexosamine in a high concentration following acid hydrolysis. The physiological significance of this mucoprotein is discussed.

A HISTOCHEMICAL AND BIOCHEMICAL STUDY OF THE POLYSACCHARIDIC SUBSTANCES OF THE DEVELOPING NERVOUS SYSTEM OF THE RAT IN RELATION WITH THE APPEARANCE OF CHOLINESTERASE ACTIVITY

1958 ◽  
Vol 36 (3) ◽  
pp. 275-288 ◽  
Author(s):  
Marc Crevier
Keyword(s):  
Nervous System ◽  
Acid Hydrolysis ◽  
Biochemical Study ◽  
Chemical Fractionation ◽  
High Concentration ◽  
Brain Substance ◽  
Pas Reaction ◽  
Irregular Action ◽  
Developing Nervous System

The PAS reaction and the cholinesterase reaction run parallel in the lower centers of the developing nervous system in the rat. Also, the two reactions appear progressively between the 10th and 15th day as the result of a chemical maturation of the neurons. Extraction of sections with methanol–chloroform does not alter the PAS reaction while acetylation inhibits it reversibly. These two facts suggest that 1,2-glycol groups are detected. Inhibition by hyaluronidase increases this evidence, despite the fact that diastase has a slight and irregular action. To elucidate the nature of the PAS reaction further, chemical fractionation of the brain substance has been attempted. (A) A fraction soluble in methanol–chloroform is metachromatic and PAS-positive in vitro. (B) A fraction soluble in a potassium chloride – potassium carbonate mixture is non-dialyzable, non-metachromatic, but PAS-positive. After acid hydrolysis it yields glucose but no hexosamine. (C) A fraction extracted from the residue by sodium hydroxide is non-dialyzable, non-metachromatic, but also PAS-positive. By chromatography and electrophoresis it is found to contain a non-sulphated mucoprotein yielding hexosamine in a high concentration following acid hydrolysis. The physiological significance of this mucoprotein is discussed.

The Teratogenic effects of salicylic acid on the developing nervous system in rats in vitro

Teratology ◽  
1993 ◽  
Vol 48 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Marion A. Joschko ◽  
Ivor E. Dreosti ◽  
Ram S. Tulsi
Keyword(s):  
Nervous System ◽  
Salicylic Acid ◽  
Teratogenic Effects ◽  
Developing Nervous System
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