Fred H. Gage – författare

This volume presents methods for the analysis of genomic variability in vertebrate neurons and broadens our knowledge in the ways we understand the brain and its neurons. The chapters in this book are divided into 5 parts, and cover the following topics: principles and approaches for discovery of somatic mosaicism in the brain, aneuploidy and ploidy variation, DNA copy number variation, LINE-1 retrotransposition, and genetic and genomic mosaicism in aging and disease. In Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory.Cutting-edge and authoritative, Genomic Mosaicism in Neurons and Other Cell Types is a valuable resource for learning about the latest techniques for the analysis of genome and genetic mosaicism in vertebrate neurons.

This volume presents methods for the analysis of genomic variability in vertebrate neurons and broadens our knowledge in the ways we understand the brain and its neurons. The chapters in this book are divided into 5 parts, and cover the following topics: principles and approaches for discovery of somatic mosaicism in the brain, aneuploidy and ploidy variation, DNA copy number variation, LINE-1 retrotransposition, and genetic and genomic mosaicism in aging and disease. In Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory.Cutting-edge and authoritative, Genomic Mosaicism in Neurons and Other Cell Types is a valuable resource for learning about the latest techniques for the analysis of genome and genetic mosaicism in vertebrate neurons.

After 40 years of research, scientists have confirmed that persistent neurogenesis occurs in the adult mammalian brain. The obvious next question is: "Are the newly generated neurons functional?" If so, "What are the functions of these new neurons?" This volume intends to clarify both questions by providing the latest data available.

The human brain is remarkably complex, permitting sophisticated behavioural rep- toires, such as languages, tool use, self-awareness, symbolic thought, cultural learning and consciousness. Each human being is different, due in part to the uniqueness of the neuronal heterogeneity and interconnections in our brains. Brain complexity and neuronal diversity are strongly related. The diversity of single neurons provides the underpinnings for how neuronal circuits operate. How and when neuronal diversity is generated, both in embryonic and adult neurogenesis, remain unknown. In the immune system, the highly diverse array of antigen receptors can be - tributed to the stochastic nature of the recombination process in somatic precursor cells, causing permanent changes in DNA and gene expression. This diverse population is then the target of selective processes that favor the correct antigen-receptor match and eliminate those with inadequate speci?cities, accounting for the rapid kinetics and immense diversity observed in vivo. Evidence for a possible similarity between the nervous and immune systems came from studies with mice de?cient in DNA double strand break (DSB) repair. Lessons learned from the discovery of the mechanism for diversityinthe immune system maybe usefultothe investigation ofthe mechanism of diversity in neurons.

The human brain is remarkably complex, permitting sophisticated behavioural rep- toires, such as languages, tool use, self-awareness, symbolic thought, cultural learning and consciousness. Each human being is different, due in part to the uniqueness of the neuronal heterogeneity and interconnections in our brains. Brain complexity and neuronal diversity are strongly related. The diversity of single neurons provides the underpinnings for how neuronal circuits operate. How and when neuronal diversity is generated, both in embryonic and adult neurogenesis, remain unknown. In the immune system, the highly diverse array of antigen receptors can be - tributed to the stochastic nature of the recombination process in somatic precursor cells, causing permanent changes in DNA and gene expression. This diverse population is then the target of selective processes that favor the correct antigen-receptor match and eliminate those with inadequate speci?cities, accounting for the rapid kinetics and immense diversity observed in vivo. Evidence for a possible similarity between the nervous and immune systems came from studies with mice de?cient in DNA double strand break (DSB) repair. Lessons learned from the discovery of the mechanism for diversityinthe immune system maybe usefultothe investigation ofthe mechanism of diversity in neurons.

The recent advances in Programming Somatic Cell (PSC) including induced Pluripotent Stem Cells (iPS) and Induced Neuronal phenotypes (iN), has changed our experimental landscape and opened new possibilities. The advances in PSC have provided an important tool for the study of human neuronal function as well as neurodegenerative and neurodevelopmental diseases in live human neurons in a controlled environment. For example, reprogramming cells from patients with neurological diseases allows the study of molecular pathways particular to specific subtypes of neurons such as dopaminergic neurons in Parkinson’s Disease, Motor neurons for Amyolateral Sclerosis or myelin for Multiple Sclerosis. Detecting disease-specific molecular signatures in live human brain cells, opens possibilities for early intervention therapies and new diagnostic tools. Importantly, once the neurological neural phenotype is detected in vitro, the so-called “disease-in-a-dish” approach allows for the screening of drugs that can ameliorate the disease-specific phenotype. New therapeutic drugs could either act on generalized pathways in all patients or be patient-specific and used in a personalized medicine approach. However, there are a number of pressing issues that need to be addressed and resolved before PSC technology can be extensively used for clinically relevant modeling of neurological diseases. Among these issues are the variability in PSC generation methods, variability between individuals, epigenetic/genetic instability and the ability to obtain disease-relevant subtypes of neurons . Current protocols for differentiating PSC into specific subtypes of neurons are under development, but more and better protocols are needed. Understanding the molecular pathways involved in human neural differentiation will facilitate the development of methods and tools to enrich and monitor the generation of specific subtypes of neurons that would be more relevant in modeling differentneurological diseases.

After 40 years of research, scientists have confirmed that persistent neurogenesis occurs in the adult mammalian brain. The obvious next question is: "Are the newly generated neurons functional?" If so, "What are the functions of these new neurons?" This volume intends to clarify both questions by providing the latest data available.

Gene transfer technology is a powerful tool for increasing our understandingof brain functions. It is also the basis of gene therapy, which is now technically possible for the correction of many human diseases, including several disorders of the nervous (and muscular) system such as Alzheimer's disease, Parkinson's disease, and dystrophy. This volume,which contains the proceedings of a symposium of the Fondation Ipsen, provides a unique view of the state of the art on different transgenes, vectors, target cells, and clinical applications related to the nervous system.

The recent advances in Programming Somatic Cell (PSC) including induced Pluripotent Stem Cells (iPS) and Induced Neuronal phenotypes (iN), has changed our experimental landscape and opened new possibilities. The advances in PSC have provided an important tool for the study of human neuronal function as well as neurodegenerative and neurodevelopmental diseases in live human neurons in a controlled environment. For example, reprogramming cells from patients with neurological diseases allows the study of molecular pathways particular to specific subtypes of neurons such as dopaminergic neurons in Parkinson’s Disease, Motor neurons for Amyolateral Sclerosis or myelin for Multiple Sclerosis. Detecting disease-specific molecular signatures in live human brain cells, opens possibilities for early intervention therapies and new diagnostic tools. Importantly, once the neurological neural phenotype is detected in vitro, the so-called “disease-in-a-dish” approach allows for the screening of drugs that can ameliorate the disease-specific phenotype. New therapeutic drugs could either act on generalized pathways in all patients or be patient-specific and used in a personalized medicine approach. However, there are a number of pressing issues that need to be addressed and resolved before PSC technology can be extensively used for clinically relevant modeling of neurological diseases. Among these issues are the variability in PSC generation methods, variability between individuals, epigenetic/genetic instability and the ability to obtain disease-relevant subtypes of neurons . Current protocols for differentiating PSC into specific subtypes of neurons are under development, but more and better protocols are needed. Understanding the molecular pathways involved in human neural differentiation will facilitate the development of methods and tools to enrich and monitor the generation of specific subtypes of neurons that would be more relevant in modeling differentneurological diseases.