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Regulation of symmetric and asymmetric cell division during brain development

大脑发育过程中对称和不对称细胞分裂的调节

基本信息

批准号：
9888448
负责人：
QIANG LU
金额：
$ 37.19万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
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：
2016-03-15 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9888448
关键词：
Adult Amino Acid Sequence Behavioral Binding Biochemical Biological Biological Assay Brain Brain Diseases Caenorhabditis elegans Cell Differentiation process Cell division Cells Cerebral cortex Complex Cues Cytokinesis Data Development Developmental Brain Malformation Diagnostic Drosophila genus Electroporation Embryo Ensure Ephrins Equilibrium Event G-Protein Signaling Pathway G-substrate GTP-Binding Protein Regulators GTP-Binding Proteins Genes Genetic Goals Homologous Gene Human Invertebrates Kinesin Knowledge Lead Link Logic Maintenance Malignant neoplasm of brain Mammals Maps Mediating Mitotic Nervous system structure Neuronal Differentiation Neurons Output Pathologic Process Protein Dynamics Proteins RGS Proteins RGS3 gene Regulation Role Shapes Signal Pathway Signal Transduction Signaling Protein Work base brain malformation cell fate specification cell type daughter cell gain of function genetic approach imaging study in utero insight live cell imaging loss of function mutant nerve stem cell neurogenesis novel novel therapeutic intervention progenitor public health relevance recruit relating to nervous system self-renewal stem stem cells tool tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Neural progenitor cells maintain a tight control of the balance between self-renewal and differentiation in the developing and adult brains and can respond to environmental cues to either switch on more proliferation or produce more differentiated cells. Such a homeostatic control is not only important for normal development but also critical for proper functioning of the brain. The long-term goal of our study is to understand how self- renewal and differentiation are regulated during brain development and to apply the obtained knowledge for developing better diagnostic tools and novel therapeutic approaches for treating developmental brain disorders and brain cancers. This application proposes to investigate a novel protein interaction network that is crucial for controlling symmetric (self-renewal) versus asymmetric (differentiation) cell division in neural progenitor cells. In our previous studies, we have demonstrated, using combined cellular, embryological, and genetic approaches, that the regulator of G protein signaling (RGS)-mediated ephrin-B reverse signaling pathway is essential for maintaining the neural progenitor cell state in the embryonic cerebral cortex and that the Ga subunit signaling pathway is important for activating neuronal differentiation. We have identified a mitotic kinesin that can interact with and recruit the ephrin B/RGS proteins into the midbody of dividing neural progenitor cells, suggesting that the role of the ephrin-B/RGS pathway in neural progenitor cell regulation is linked to cytokinesis, the final stage of cell division. In addition, we have recently identified several interacting proteins of th active Ga subunits and found that these proteins, similar to Gα subunit, could activate neurogenesis. We thus propose to further characterize the biochemical interaction of the ephrin-B/RGS/mitotic kinesin and Ga subunit interaction network and examine the potential function of these networks in shaping neural progenitor cells' decision to either divide symmetrically or asymmetrically. We anticipate that the data obtained from this study will ultimately help understand what and how molecular interactions in neural progenitor cells guides the balance between self-renewal and differentiation and how dysregulation in these networks may lead to certain developmental brain disorders or tumorigenesis.

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development.

DOI：
10.1038/s41467-018-05152-1
发表时间：
2018-07-13
期刊：
Nature communications
影响因子：
16.6
作者：
Geng A;Qiu R;Murai K;Liu J;Wu X;Zhang H;Farhoodi H;Duong N;Jiang M;Yee JK;Tsark W;Lu Q
通讯作者：
Lu Q

Depletion of kinesin motor KIF20A to target cell fate control suppresses medulloblastoma tumour growth.