{"title":"Introduction: Use of genetically-manipulated mice for investigation of the nervous system","authors":"H. Phillips","doi":"10.1006/SMNS.1996.0015","DOIUrl":"https://doi.org/10.1006/SMNS.1996.0015","url":null,"abstract":"","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"29 1","pages":"115-116"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72948207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction: Use of genetically-manipulated mice for investigation of the nervous system","authors":"Heidi Phillips","doi":"10.1006/smns.1996.0015","DOIUrl":"https://doi.org/10.1006/smns.1996.0015","url":null,"abstract":"<div><p>No abstract</p></div>","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"8 3","pages":"Pages 115-116"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smns.1996.0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91654912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Freda D. Miller , David Rogers , Shernaz X. Bamji , Ruth S. Slack , Andrew Gloster
Analysis of the molecular genetic mechanisms underlying neuronal differentiation in mammals has been hampered by the lack of appropriate model systems. Here, we review the evidence that the Tα1 α-tubulin gene represents such a model system. The endogenous Tα1 gene is expressed at highly abundant levels during the growth of developing and mature neurons. In transgenic mice, 1·1 kb of 5′ flanking sequence from the Tα1 gene is sufficient to target gene expression to early developing neurons, and to regulate levels of expression as a function of neuronal growth. Analysis of this promoter has led to the initial elucidation of sequence elements essential for gene expression during neuronal development. Moreover, the Tα1 promoter provides an experimental mechanism for the manipulation and analysis of differentiating neurons in transgenic mice.
{"title":"Analysis and manipulation of neuronal gene expression using the Tα1 α-tubulin promoter","authors":"Freda D. Miller , David Rogers , Shernaz X. Bamji , Ruth S. Slack , Andrew Gloster","doi":"10.1006/smns.1996.0016","DOIUrl":"https://doi.org/10.1006/smns.1996.0016","url":null,"abstract":"<div><p>Analysis of the molecular genetic mechanisms underlying neuronal differentiation in mammals has been hampered by the lack of appropriate model systems. Here, we review the evidence that the Tα1 α-tubulin gene represents such a model system. The endogenous Tα1 gene is expressed at highly abundant levels during the growth of developing and mature neurons. In transgenic mice, 1·1 kb of 5′ flanking sequence from the Tα1 gene is sufficient to target gene expression to early developing neurons, and to regulate levels of expression as a function of neuronal growth. Analysis of this promoter has led to the initial elucidation of sequence elements essential for gene expression during neuronal development. Moreover, the Tα1 promoter provides an experimental mechanism for the manipulation and analysis of differentiating neurons in transgenic mice.</p></div>","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"8 3","pages":"Pages 117-124"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smns.1996.0016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90008032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Miller, D. Rogers, S. Bamji, R. Slack, A. Gloster
Abstract Analysis of the molecular genetic mechanisms underlying neuronal differentiation in mammals has been hampered by the lack of appropriate model systems. Here, we review the evidence that the Tα1 α-tubulin gene represents such a model system. The endogenous Tα1 gene is expressed at highly abundant levels during the growth of developing and mature neurons. In transgenic mice, 1·1 kb of 5′ flanking sequence from the Tα1 gene is sufficient to target gene expression to early developing neurons, and to regulate levels of expression as a function of neuronal growth. Analysis of this promoter has led to the initial elucidation of sequence elements essential for gene expression during neuronal development. Moreover, the Tα1 promoter provides an experimental mechanism for the manipulation and analysis of differentiating neurons in transgenic mice.
{"title":"Analysis and manipulation of neuronal gene expression using the Tα1 α-tubulin promoter","authors":"F. Miller, D. Rogers, S. Bamji, R. Slack, A. Gloster","doi":"10.1006/SMNS.1996.0016","DOIUrl":"https://doi.org/10.1006/SMNS.1996.0016","url":null,"abstract":"Abstract Analysis of the molecular genetic mechanisms underlying neuronal differentiation in mammals has been hampered by the lack of appropriate model systems. Here, we review the evidence that the Tα1 α-tubulin gene represents such a model system. The endogenous Tα1 gene is expressed at highly abundant levels during the growth of developing and mature neurons. In transgenic mice, 1·1 kb of 5′ flanking sequence from the Tα1 gene is sufficient to target gene expression to early developing neurons, and to regulate levels of expression as a function of neuronal growth. Analysis of this promoter has led to the initial elucidation of sequence elements essential for gene expression during neuronal development. Moreover, the Tα1 promoter provides an experimental mechanism for the manipulation and analysis of differentiating neurons in transgenic mice.","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"51 1","pages":"117-124"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81414715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Single gene manipulation allows one to create mutant mammalian organisms that may be useful for genetic dissection of mechanisms underlying brain function and behavior. Alterations in a mutant organism may be directly related to the mutation or due to compensatory mechanisms. Analysis of these responses may reveal molecular organization of the brain. However, the results of several recent molecular neurobiology studies are difficult to interpret since they are flawed by the problems resulting from genetic linkage of and variability in background genes. The behavioral analysis of mutant mice may also be uninterpretable if one ignores species-specific characteristics of the experimental animals.
{"title":"Molecular genetic analysis of mammalian behavior and brain processes: caveats and perspectives","authors":"R. Gerlai","doi":"10.1006/SMNS.1996.0020","DOIUrl":"https://doi.org/10.1006/SMNS.1996.0020","url":null,"abstract":"Abstract Single gene manipulation allows one to create mutant mammalian organisms that may be useful for genetic dissection of mechanisms underlying brain function and behavior. Alterations in a mutant organism may be directly related to the mutation or due to compensatory mechanisms. Analysis of these responses may reveal molecular organization of the brain. However, the results of several recent molecular neurobiology studies are difficult to interpret since they are flawed by the problems resulting from genetic linkage of and variability in background genes. The behavioral analysis of mutant mice may also be uninterpretable if one ignores species-specific characteristics of the experimental animals.","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"86 1","pages":"153-161"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83074467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our understanding of patterning along the dorsoventral (DV) axis has been advanced by embryological studies which have allowed the identification of dorsal and ventral organizing centers, and of molecular signals that can actin vitroto specify cell fate. However, in order to establish anin-vivorole for a signal it is necessary to show that the molecule is present in the right place and time, that exogenous addition or ectopic expression of the signal mimics its proposed effect and that deletion of its activity results in an absence of the presumed biological response. Such evidence can be provided by gene deletion (knock-out) or ectopic expression (transgenic) studies. In this review, experimental embryological studies that have increased our understanding of DV patterning will be discussed, and studies in which gene manipulation has provided evidence about the in-vivo role of a molecule will be highlighted.
{"title":"The contribution of gene manipulation techniques to understanding dorsoventral patterning in the vertebrate nervous system","authors":"M. Hynes, A. Rosenthal","doi":"10.1006/SMNS.1996.0017","DOIUrl":"https://doi.org/10.1006/SMNS.1996.0017","url":null,"abstract":"Our understanding of patterning along the dorsoventral (DV) axis has been advanced by embryological studies which have allowed the identification of dorsal and ventral organizing centers, and of molecular signals that can actin vitroto specify cell fate. However, in order to establish anin-vivorole for a signal it is necessary to show that the molecule is present in the right place and time, that exogenous addition or ectopic expression of the signal mimics its proposed effect and that deletion of its activity results in an absence of the presumed biological response. Such evidence can be provided by gene deletion (knock-out) or ectopic expression (transgenic) studies. In this review, experimental embryological studies that have increased our understanding of DV patterning will be discussed, and studies in which gene manipulation has provided evidence about the in-vivo role of a molecule will be highlighted.","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"63 1","pages":"125-131"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80137759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Wong, D. Borchelt, Michael K. Lee, C. Pardo, S. Sisodia, D. Cleveland, V. Koliatsos, D. Price
Abstract The motor neuron diseases (MND) are an etiologically heterogeneous group of disorders characterized by weakness and muscle atrophy. These clinical signs are attributable to the involvement of lower motor neurons; the presence of spasticity and hyperreflexia indicates involvement of upper motor neurons. Depending on the characteristics of the disease process, vulnerable cells develop inclusions, alterations in the cytoskeleton, etc., before undergoing cell death. Over the past several years, significant progress has been made in understanding the genetics of some of these disorders, including familial amyotrophic lateral sclerosis (FALS), spinal muscular atrophy (SMA), and spinal bulbar muscular atrophy (SBMA). For example, some of the autosomal dominant cases of FALS are linked to mutations in the superoxide dismutase 1 (SOD1) gene. Several groups have introduced these SOD1 mutations into transgenic mice, and these animals develop features of the human disease. Other investigators have used transgenic strategies to overexpress wild-type (wt) or mutant neurofilament (NF) genes, and some of these mice show abnormalities of the neuronal cytoskeleton that resemble those occurring in sporadic amyotrophic lateral sclerosis (ALS). Finally, in efforts to define trophic influences on these cells, investigators have used gene-targeting strategies to ablate genes coding for these factors or their receptors and to assess the consequences of the null state on behavior and cell phenotype. This review outlines some of the progress that has been made in modeling disorders of motor neurons, either by introducing mutant SOD1 transgenes or by overexpressing wt or mutant NF genes, and the recent advances made using gene-targeting strategies to define trophic dependencies of motor neurons.
{"title":"Transgenic and gene-targeting approaches to model disorders of motor neurons","authors":"P. Wong, D. Borchelt, Michael K. Lee, C. Pardo, S. Sisodia, D. Cleveland, V. Koliatsos, D. Price","doi":"10.1006/SMNS.1996.0021","DOIUrl":"https://doi.org/10.1006/SMNS.1996.0021","url":null,"abstract":"Abstract The motor neuron diseases (MND) are an etiologically heterogeneous group of disorders characterized by weakness and muscle atrophy. These clinical signs are attributable to the involvement of lower motor neurons; the presence of spasticity and hyperreflexia indicates involvement of upper motor neurons. Depending on the characteristics of the disease process, vulnerable cells develop inclusions, alterations in the cytoskeleton, etc., before undergoing cell death. Over the past several years, significant progress has been made in understanding the genetics of some of these disorders, including familial amyotrophic lateral sclerosis (FALS), spinal muscular atrophy (SMA), and spinal bulbar muscular atrophy (SBMA). For example, some of the autosomal dominant cases of FALS are linked to mutations in the superoxide dismutase 1 (SOD1) gene. Several groups have introduced these SOD1 mutations into transgenic mice, and these animals develop features of the human disease. Other investigators have used transgenic strategies to overexpress wild-type (wt) or mutant neurofilament (NF) genes, and some of these mice show abnormalities of the neuronal cytoskeleton that resemble those occurring in sporadic amyotrophic lateral sclerosis (ALS). Finally, in efforts to define trophic influences on these cells, investigators have used gene-targeting strategies to ablate genes coding for these factors or their receptors and to assess the consequences of the null state on behavior and cell phenotype. This review outlines some of the progress that has been made in modeling disorders of motor neurons, either by introducing mutant SOD1 transgenes or by overexpressing wt or mutant NF genes, and the recent advances made using gene-targeting strategies to define trophic dependencies of motor neurons.","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"40 1","pages":"163-169"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80148255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction: From growth cone to synapse","authors":"Philip G. Haydon","doi":"10.1006/smns.1996.0009","DOIUrl":"10.1006/smns.1996.0009","url":null,"abstract":"<div><p>No abstract</p></div>","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"8 2","pages":"Page 65"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smns.1996.0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89819098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The developing neuromuscular junction provides a simple system for understanding the cellular and molecular events that transform a growth cone into a nerve terminal. Molecules on the surface and within the extracellular matrix of the skeletal muscle cell provide cues for presynaptic differentiation which culminates in the development of presynaptic specializations. Growth factors bound to the heparan-sulfate proteoglycan on the muscle surface have been implicated as signals for the induction of these specializations. Upon reaching the target, the nerve may secrete a molecule to cause the local release of these factors, which then activate receptor tyrosine kinases on the neuronal membrane. This process may lead to the assembly of a cytoskeletal specialization to effect the clustering of synaptic vesicles and the organization of the presynaptic membrane.
{"title":"From neurite to nerve terminal: induction of presynaptic differentiation by target-derived signals","authors":"Zhengshan Dai, Benjamin H. Peng","doi":"10.1006/smns.1996.0013","DOIUrl":"10.1006/smns.1996.0013","url":null,"abstract":"<div><p>The developing neuromuscular junction provides a simple system for understanding the cellular and molecular events that transform a growth cone into a nerve terminal. Molecules on the surface and within the extracellular matrix of the skeletal muscle cell provide cues for presynaptic differentiation which culminates in the development of presynaptic specializations. Growth factors bound to the heparan-sulfate proteoglycan on the muscle surface have been implicated as signals for the induction of these specializations. Upon reaching the target, the nerve may secrete a molecule to cause the local release of these factors, which then activate receptor tyrosine kinases on the neuronal membrane. This process may lead to the assembly of a cytoskeletal specialization to effect the clustering of synaptic vesicles and the organization of the presynaptic membrane.</p></div>","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"8 2","pages":"Pages 97-106"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smns.1996.0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83873760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Pathfinding decisions, as neuronal growth cones navigate their complex embryonic terrain, are largely determined by the fan-shaped array of filopodia at the leading edge of the advancing growth cone. These sensory/motor extensions of growth cones locally receive, process, and react to information from their environment. Recent advances in our knowledge of the mechanisms by which extracellular signals cause changes in the concentration of the second messenger calcium and by which calcium affects growth cone function have provided substantial insights into the chain of events occurring in filopodia that help guide growth cones to their appropriate targets.
{"title":"Filopodia on neuronal growth cones: multi-functional structures with sensory and motor capabilities","authors":"Vincent Rehder , Stanley B. Kater","doi":"10.1006/smns.1996.0011","DOIUrl":"10.1006/smns.1996.0011","url":null,"abstract":"Abstract Pathfinding decisions, as neuronal growth cones navigate their complex embryonic terrain, are largely determined by the fan-shaped array of filopodia at the leading edge of the advancing growth cone. These sensory/motor extensions of growth cones locally receive, process, and react to information from their environment. Recent advances in our knowledge of the mechanisms by which extracellular signals cause changes in the concentration of the second messenger calcium and by which calcium affects growth cone function have provided substantial insights into the chain of events occurring in filopodia that help guide growth cones to their appropriate targets.","PeriodicalId":101157,"journal":{"name":"Seminars in Neuroscience","volume":"8 2","pages":"Pages 81-88"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smns.1996.0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73985007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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