PREDOCTORAL FELLOWSHIPS FOR STUDENTS WITH DISABILITIES

为残疾学生提供博士前奖学金

基本信息

批准号：
7197342
负责人：
Heather DiPietrantonio
金额：
$ 2.79万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-01-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7197342
关键词：
Address Adult Affect Biological Assay Birth Brain Brain Stem Brain region Candidate Disease Gene Cell Adhesion Molecules Cell Cycle Cell Nucleus Cell Separation Cell division Cells Central Nervous System Diseases Cerebral cortex Class Classification Competence Data Data Set Development Distant Dominant-Negative Mutation Dorsal Electroporation Embryo Emigrations Event Expressed Sequence Tags Fellowship Gene Expression Gene Expression Profile Generations Genes Genetic Genome Goals In Situ Individual Intrinsic factor Investigation Knock-out Left Lip structure Messenger RNA Methods Mitosis Mitotic Modeling Modification Molecular Molecular Profiling Names Nature Neonatal Nervous system structure Neuroglia Neurons Neurotransmitters Pattern Phenotype Physiological Predoctoral Fellowship--Students with Disabilities Production Protein Overexpression Proteins RNA Interference Radial Retina Role SAGE Library Screening procedure Site Sorting - Cell Movement Staging Stem cells Stream Sudden infant death syndrome System Taxonomy Testing Time Tissues Validation Work base cell motility cell type cohort developmental neurobiology direct application hindbrain histogenesis in vivo interest knock-down loss of function neurochemistry neurogenesis progenitor programs receptor recombinase relating to nervous system selective expression transcription factor

项目摘要

DESCRIPTION (provided by applicant): Understanding how neuron subtypes are generated from a proliferative zone in the developing brain is a primary goal in the field of developmental neurobiology. A germinal zone in the dorsal hindbrain, the rhombic lip, gives rise sequentially to six topographically separate and ventrally-located nuclei, collectively termed the precerebellar system. We hypothesize that the transcriptional profile in the rhombic lip changes over time, and that these changes underlie, at least in part, this sequential specification and allocation of precerebellar subtypes. To test this, we are generating statistical representations of the rhombic lip transcriptome (genome-wide) at sequential time points, as well as transcriptomes of mature precerebellar nuclei. By analyzing this set of transcriptomes for mRNAs that correlate with the emergence of specific cell types, we have identified candidate specification/sorting genes that now require validation. In Aim 1, we will validate by in situ mRNA hybridization approximately 500 candidate genes. In Aim 2, we will establish a set of markers that break the rhombic lip and the mature precerebellar nuclei into molecularly distinct subpopulations. In Aim 3, we will analyze a handful of the most promising candidates for their functional role in cell fate determination. Remarkably, precerebellar development has been understudied yet has been associated with SIDS and many other CNS disorders.

描述（由申请人提供）：了解神经元亚型如何从发育中的大脑的增殖区产生是发育神经生物学领域的主要目标。背侧后脑的生发区，即菱形唇，依次产生六个地形上独立且位于腹侧的核团，统称为小脑前系统。我们假设菱形唇中的转录谱随着时间的推移而变化，并且这些变化至少部分地构成了小脑前亚型的这种顺序规范和分配的基础。为了测试这一点，我们正在连续时间点生成菱形唇转录组（全基因组）的统计表示，以及成熟小脑前核的转录组。通过分析这组与特定细胞类型的出现相关的 mRNA 转录组，我们已经确定了现在需要验证的候选规范/分选基因。在目标 1 中，我们将通过原位 mRNA 杂交验证大约 500 个候选基因。在目标 2 中，我们将建立一组标记，将菱形唇和成熟的小脑前核分解为分子上不同的亚群。在目标 3 中，我们将分析一些最有前途的候选者，了解它们在细胞命运决定中的功能作用。值得注意的是，小脑前发育尚未得到充分研究，但它与 SIDS 和许多其他中枢神经系统疾病有关。