权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanisms Driving Regenerative Neurogenesis in Planarians

涡虫再生神经发生的驱动机制

基本信息

批准号：
10641949
负责人：
Rachel Helen Roberts-Galbraith
金额：
$ 37.75万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-15 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10641949
关键词：
Acetylcholine Adult Animals Anterior Automobile Driving Behavior Behavioral Assay Biological Assay Brain Cells Central Nervous System Cephalic Complex Cues Development Dopamine Dorsal Failure Fresh Water Ganglia Genes Glutamates Goals Health Homeostasis Human Injury Laboratories Location Maintenance Modeling Molecular Movement Muscle Natural regeneration Nature Nerve Nerve Regeneration Nerve Tissue Nervous System Neurobiology Neurodegenerative Disorders Neuroglia Neurons Neuropeptides Neurotransmitters Organ Outcome Partner in relationship Pathway interactions Patients Pattern Peripheral Nervous System Pharyngeal structure Planarians Platyhelminths Pluripotent Stem Cells Positioning Attribute Predatory Behavior Recovery Regenerative research Regulation Research Rest Role Serotonin Signal Induction Signal Transduction Spinal Cord Spinal cord injury Stem cell transplant Stimulus Stroke Structure Testing Tissues Traumatic injury Work adult stem cell brain tissue cell injury cell type dopaminergic neuron feeding functional restoration gamma-Aminobutyric Acid improved in vivo injury and repair innovation ischemic injury model organism neural neural repair neurogenesis neuron regeneration novel therapeutic intervention post stroke reconstitution regeneration model regenerative regenerative therapy repaired response response to injury stem cell differentiation stem cell therapy tissue regeneration transcription factor wound

项目摘要

Project Summary Humans regenerate tissue of the brain and spinal cord poorly. Failure to regenerate missing or damaged cells impedes survival and recovery after neurodegenerative disease, stroke, traumatic or ischemic injury, or developmental error. Unlike humans, other animals can effectively repair dramatic injuries or damage within the central nervous system. Free-living freshwater flatworms called planarians possess extraordinary regenerative abilities, including flawless regeneration and replacement of all brain and nerve cord tissues. After tissue loss or damage, planarians remodel existing tissue and use adult pluripotent stem cells to replace diverse cell types, including dozens of types of neurons. Planarians create neurons in appropriate ratios and then repattern and reconnect neurons to targets to restore function. The long-term goal is to discover the molecular and cellular basis of robust neural regeneration using planarians. Toward that objective, the first specific aim is to identify and characterize factors important for regenerative neurogenesis from pluripotent stem cells, focusing first on regeneration of dopaminergic neurons. Four transcription factor-encoding genes important for regeneration and maintenance of dopaminergic neuron subtypes have already been discovered. The following specific aims will provide critical information about how environmental cues promote brain regeneration by pluripotent stem cells in vivo. The second specific aim is to test the hypothesis that neurogenesis is upregulated in planarians after injury, through wound-induced signaling mechanisms. The third specific aim is to test the hypothesis that planarian neurogenesis is driven by polarity cues so that new neurons of the correct types are created in the proper locations. The proposed work in this application is conceptually innovative because of the use of a highly regenerative model organism to explore regenerative neurogenesis and because of the development of new molecular and behavioral assays (e.g. DAP-Seq, live prey assays). The proposed research is significant because it will provide a foundational understanding of successful neural regeneration in response to injury, with a long-term goal of identifying pathways or molecular mechanisms that could be leveraged to improve human regenerative therapies.

项目总结