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Demographics of Retinal Nerve Cell Populations

视网膜神经细胞群的人口统计学

基本信息

批准号：
9884059
负责人：
BENJAMIN E REESE
金额：
$ 38.83万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884059
关键词：
Address Affect Age Alternative Splicing Amacrine Cells Architecture Automobile Driving Binding Biological Assay Biological Models Candidate Disease Gene Cell Count Cell Differentiation process Cells Code Dependence Development Developmental Process Eye diseases Family Family member Gene Expression Gene Family Genes Genetic Genetic Determinism Genetic Variation In Vitro Inbred Strains Mice Interneurons Knockout Mice Luciferases Maps Messenger RNA Microarray Analysis Molecular Molecular Genetics Morphology Mosaicism Mouse Strains NFIA gene Nervous system structure Neurons Pattern Play Population Population Dynamics Population Sizes Positioning Attribute Process Property Protein Isoforms Proteins Quantitative Trait Loci RNA Recognition Motif RNA Splicing RNA-Binding Proteins Recombinants Regenerative Medicine Regulation Reporter Research Research Proposals Retina Role SLC17A8 gene Source Spliced Genes Territoriality Testing Tissues Transcript Transgenic Organisms Variant causal variant cell type chromatin immunoprecipitation conditional knockout demographics density developmental disease gene function genetic variant genomic locus horizontal cell in vivo knockout gene knowledge base loss of function member nervous system disorder novel programs relating to nervous system retinal neuron selective expression statistics trait transcription factor

项目摘要

ABSTRACT Cellular populations in the nervous system vary in their demographics: They differ in their size, positioning, intercellular spacing, dendritic overlap, and connectivity. This research program has been identifying the genetic sources of this variation and analyzing the interdependencies between these population dynamics, using the retina as a model system and a panel of twenty-six genetically distinct recombinant inbred mouse strains. Neuron number varies considerably across these strains of mice, for every different type of retinal neuron analyzed to date, and this variation maps to discrete and largely independent genomic loci for each cell type, showing minimal evidence for genetic co-regulation. The present proposal will continue to explore the genetic sources of such variation in cell number, focusing upon different populations of retinal interneurons, and how such variation in their cell number affects those other demographic traits, via four new specific aims. Specific Aim 1 will extend our use of quantitative trait locus (QTL) mapping strategies to identify epistatic interactions controlling the variation in retinal cell number. It will identify candidate genes at interacting genomic loci, and demonstrate their genetic interaction directly. Specific Aim 2 will examine the role of the Rbfox gene family in retinal development, and identify changes in alternative splice transcripts in the absence of RBFOX function. Specific Aim 3 will define the role of the transcription factor, Nfia, in the selective control of AII amacrine cell number. It will assess the alternative splicing of Nfia as a function of development, and examine the functional properties of developmentally regulated isoforms. Specific Aim 4 will define the degree of dependency of VGluT3 amacrine cell differentiation upon the density and intercellular spacing of these cells, seeking to understand the role played by homotypic interactions in regulating retinal coverage. The present research proposal will thereby identify the genetic determinants and intercellular interactions that underlie the demographic features of cellular populations in the retina. These studies will clarify our understanding of retinal development and identify novel genes and their variants that may contribute to developmental disorders of the nervous system, together informing the emerging field of regenerative medicine.

摘要