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

The developmental origins and fate of neurons in the gyrencephalic neocortex

环脑新皮质神经元的发育起源和命运

基本信息

批准号：
10429019
负责人：
Tarik F Haydar
金额：
$ 26.78万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
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：
2022-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10429019
关键词：
Anatomy Applications Grants Brain Cells Comparative Study Complex Data Data Set Development Dorsal Electroporation Etiology Family suidae Ferrets Gene Delivery Gene Expression Generations Genetic Genomics Goals Growth Human Imaging Techniques Infant Label Laboratories Methods Miniature Swine Modeling Modernization Molecular Molecular Profiling Monkeys Morphology Mus Neocortex Neurodevelopmental Disorder Neuroglia Neurons Operative Surgical Procedures Pilot Projects Plasmids Play Pongidae Population Primates Process Radial Rattus Rodent Role Slice Sus scrofa System Techniques Time Ventricular Work base cell type cellular imaging cognitive ability density fetal fluorescence imaging frontal lobe genetic manipulation in utero in vivo interdisciplinary approach lissencephaly neocortical nerve stem cell neurophysiology perinatal period porcine model postnatal precursor cell prenatal progenitor protein biomarkers self-renewal single cell sequencing skills subventricular zone tool transcriptomics treatment strategy

项目摘要

SUMMARY/ABSTRACT: Diverse networks of neurons and glia produce the advanced computational power of the mammalian brain. Neural precursor cell (NPC) populations present in the ventricular and subventricular zones (VZ and SVZ) of the prenatal brain generate all neurons and glia either directly, or indirectly via intermediate progenitors. While there has been a rapid increase in understanding the cell diversity and underlying genetic mechanisms of these precursor cells, most of this work has been accomplished in the lissencephalic rodent. Some recent findings in gyrencephalic species indicate that NPC types and their developmental mechanisms are tuned differently in species with larger brains. For example, recent studies have discovered that, unlike in rodents, the density of basal radial glial cells (bRGCs) is significantly higher in primate brain, but the neuroanatomical and neurophysiological advantage(s) of this difference have not been established. Similarly, large numbers of neurons migrating to the frontal lobe are present in the human infant brain but are not found in mouse; neither the mechanisms underlying their prenatal generation nor their processes of integration into the neocortex have been identified. While single cell transcriptomic data has opened new windows into the gene expression underlying this diversity, the ability to not only confirm species-specific differences but to also interrogate their effects in vivo is hampered by the lack of an appropriate model. Piglets are a powerful model with which to study complex brain development because they have a highly evolved gyrencephalic neocortex. Our previous studies found that the cytoarchitecture of the porcine SVZ is exceptionally similar to its human counterpart. Consistent with the human infant cortex, young neurons in the piglet SVZ migrate to the frontal cortex and differentiate into neurons in a region-specific manner. Finally, our recent collaborative single cell sequencing study has uncovered cell populations with unique molecular profiles within the piglet SVZ that are not found in rodent SVZ. Thus, we hypothesize that elucidating the diversity and fate potential of the porcine VZ and SVZ neural precursors will accelerate our understanding of human neuronal diversity, cortical circuit complexity and cognitive ability. Our project will establish an in vivo gene delivery method to visualize NPC dynamics and neuronal specification in the fetal piglet VZ and SVZ (Aim 1); and visualize late-migrating neurons and cell populations derived from the postnatal piglet SVZ (Aim 2). Establishment of a system in which a large gyrencephalic brain can be studied using modern genetic and cellular imaging techniques would significantly impact our understanding of normal human brain development and provide a critical tool for elucidating the etiology for neurodevelopmental disorders. This advance will enable key comparative studies with other datasets from gyrencephalic and lissencephalic species and allow genomic/cellular understanding of early brain development in a model that shares important developmental and anatomical similarities to the human brain.

摘要/文摘: