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

Regulating retinal cell fate with microRNAs

用 microRNA 调节视网膜细胞命运

基本信息

批准号：
9027093
负责人：
DAVID L TURNER
金额：
$ 38.75万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9027093
关键词：
Adult Affect Amacrine Cells Biochemical Blindness CRISPR/Cas technology Cell Fate Control Cell Lineage Cell physiology Cells Cellular biology Clustered Regularly Interspaced Short Palindromic Repeats Complex Data Development Electroporation Embryo Future Gene Targeting Generations Genes Genetic Health Health Care Costs Human Individual Injury Inner Nuclear Layer Interneurons Intervention Knockout Mice Lead Mammals Mediating Messenger RNA MicroRNAs Molecular Morphology Mus Neonatal Neuraxis Neurons Neurotransmitters Pathway interactions Patients Post-Transcriptional Regulation Quality of life RNA Regulation Regulatory Pathway Retina Retinal Retinal Diseases Role Signal Pathway Somatic Cell Stem Cell Research Stem cells Structure Thiouracil Tissues Visual Perception Visual impairment Work base cell type crosslink design economic cost horizontal cell improved in vivo insight mRNA Expression migration molecular marker novel postnatal precursor cell programs public health relevance relating to nervous system repaired retinal damage retinal regeneration transcription factor vector

项目摘要

DESCRIPTION (provided by applicant): Blindness and impaired vision arising from retinal disease or damage are health problems with substantial human and economic costs. Recent advances in stem cell research suggest that retinal repair in humans will be feasible in the foreseeable future. However our understanding of retinal cell biology and development remains incomplete, limiting rational design of repair strategies. Cellular complexity is a key feature of the mammalian central nervous system, including the retina. The retina contains more than 50 different types of neurons, based on morphology, neurotransmitters, and other molecular markers. Cascades of transcription factors and various signaling pathways have been implicated in retinal cell type determination and the generation of cellular diversity in the retin. Recent studies have also implicated post-transcriptional regulation by microRNAs in the control of retinal cell identity. We have identified two related miRNAs that alter retinal development and promote amacrine interneuron formation, at the expense of other retinal cell types, when ectopically expressed in the developing mouse retina. We have used Argonaute PAR-CLIP to identify endogenous target mRNAs for these and other miRNAs in the neonatal mouse retina. Here we propose to determine the requirements for these miRNAs in amacrine cell formation, using CRISPR technology in retinas. We also plan to analyze a candidate target gene for its role in the regulation of retinal development, and we propose to analyze changes in mRNA expression to identify molecular and cellular pathways in the retina that are affected by these miRNAs. Finally, we propose to investigate the scope of miRNA regulation in retinal cells expressing the Ptf1a transcription factor, which is required for amacrine and horizontal cell formation. These studies will provide insight into the molecular mechanisms that control development and cell fate determination in the mammalian retina. They are expected to provide information that will contribute to new strategies to repair retinal tissue.