Derivation of GABAergic interneurons from mouse embryonic stem cells

从小鼠胚胎干细胞中衍生出 GABA 能中间神经元

基本信息

批准号：
7676876
负责人：
Asif Mirza Maroof
金额：
$ 2.83万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-20 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7676876
关键词：
Adult Albumins Autistic Disorder Brain Cell Line Cell Separation Cell Therapy Cell Transplantation Cell Transplants Cells Cerebral cortex Chronic Derivation procedure Destinations Development Disease Disease model ES Cell Line Embryo Engineering Environment Epilepsy Erinaceidae Fibroblast Growth Factor 8 Generations Goals Green Fluorescent Proteins Injection of therapeutic agent Interneurons Learning Medial Memory Mental disorders Methods Mitotic Modification Morphology Movement Mus Neocortex Neonatal Neurologic Neurons Nodal Pan Genus Partial Epilepsies Pattern Perception Pharmaceutical Preparations Play Population Production Promoter Regions Protocols documentation Publishing Relative (related person)Research Resistance Rodent Role Schizophrenia Site Somatostatin Source Staging Structure Subgroup System Techniques Telencephalon Testing Tetracyclines Therapeutic Agents Transactivation Transgenic Organisms Transplantation base embryonic stem cell gamma-Aminobutyric Acid inhibitor/antagonist migration morphogens nerve stem cell neurochemistry neuropsychiatry neurotransmission postnatal progenitor promoter repaired research study stem tool transcription factor

Adult Albumins Autistic Disorder Brain Cell Line Cell Separation Cell Therapy Cell Transplantation Cell Transplants Cells Cerebral cortex Chronic Derivation procedure Destinations Development Disease Disease model ES Cell Line Embryo Engineering Environment Epilepsy Erinaceidae Fibroblast Growth Factor 8 Generations Goals Green Fluorescent Proteins Injection of therapeutic agent Interneurons Learning Medial Memory Mental disorders Methods Mitotic Modification Morphology Movement Mus Neocortex Neonatal Neurologic Neurons Nodal Pan Genus Partial Epilepsies Pattern Perception Pharmaceutical Preparations Play Population Production Promoter Regions Protocols documentation Publishing Relative (related person)Research Resistance Rodent Role Schizophrenia Site Somatostatin Source Staging Structure Subgroup System Techniques Telencephalon Testing Tetracyclines Therapeutic Agents Transactivation Transgenic Organisms Transplantation base embryonic stem cell gamma-Aminobutyric Acid inhibitor/antagonist migration morphogens nerve stem cell neurochemistry neuropsychiatry neurotransmission postnatal progenitor promoter repaired research study stem tool transcription factor

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项目摘要

DESCRIPTION (provided by applicant): By providing the major source of inhibitory circuitry in the cerebral cortex, GABAergic neurons are required for the synchronous activity necessary to generate sustained oscillations among neurons within a network that are essential during perception, coordinated movement, learning and memory. Cortical deficits in inhibitory neuronal transmission have been implicated in neuropsychiatric disorders such as epilepsy, autism, and schizophrenia. Generating a limitless supply of GABAergic neurons from would allow for the extensive use of these cells in a variety of disease models in order to evaluate their potential for use in cell based therapies. The goal of this proposal is to generate cortical GABAergic interneurons from mouse embryonic stem (ES) cells. Using modifications of published protocols, I will first optimize the production of telencephalic (FoxG1+) progenitors that co-express Nkx2.1, a transcription factor that is required for the specification of major subgroups of cortical interneurons in rodents. Since Nkx2.1 also gives rise to other populations of subcortically generated cells, I have generated an ES cell line that expresses green fluorescent protein under control of the promoter region of Lhx6, a transcription factor whose expression is enriched within Nkx2.1-lineage interneuron precursors and maintained in most of these cells through postnatal development. Using this and other tools, I will direct ES cells towards putative interneuron progenitor (mitotic) or precursor (postmitotic, but not yet migrated into cortex) states and test their capacity to migrate, survive, and differentiate within postnatal mouse cortex. These experiments could have important implications for cell based therapies for medication resistant chronic focal epilepsy. In addition, successful derivation of Nkx2.1-lineage interneuron's from ES cells would provide an invaluable system for the study of intrinsic and extrinsic factors regulating the development of these critical neurons.