Developmental genetics of neural stem cells

神经干细胞的发育遗传学

• 批准号: 10241298
• 负责人: KRISHNA MOORTHI BHAT
• 金额: $ 29.9万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-16 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241298
• 关键词: 3' Untranslated Regions; Address; Alleles; Apoptosis; Automobile Driving; Biology; CCNE1 gene; Cell Cycle; Cell Cycle Regulation; Cell division; Cells; Chromosomes; Complex; DNA biosynthesis; Development; Drosophila genus; Entropy; Environment; Genes; Genetic; Grant; Length; Link; Malignant Neoplasms; Measures; Mediating; Messenger RNA; Monitor; Mutation; Nerve; Nervous system structure; Neurons; Nuclear; Organism; Organogenesis; Play; Process; Protein Family; Proteins; Regulation; Rest; Role; Somatic Cell; Specific qualifier value; System; Telomere Shortening; Testing; Thermodynamics; Time; To specify; Work; developmental genetics; fly; gain of function mutation; gene cloning; loss of function; mRNA Transcript Degradation; member; mutant; nerve stem cell; neuroblast; precursor cell; prevent; self-renewal; telomere; tool

Abstract In the Drosophila nerve cord, neuronal precursor cells called neuroblasts (NBs) undergo a variable number of self-renewing asymmetric divisions. At some point during development, these cells either become quiescent but re-enter cell cycle later, terminally divide into neurons, or undergo apoptosis. No one knows whether these precursors measure elapsed time or count the number of divisions before exiting the cell-cycle. In the fly nervous system, NBs differ in their division potential--the number of times they undergo division. NBs must decide to enter or exit from the cell cycle, but whether their read out is the time elapsed or a cell cycle count is unknown. Additionally, we do not know whether the mechanism(s) is regulated from within the cell or extrinsic to the cell. These are difficult questions to address. By examining different types of NBs, we hope to reveal genes and mechanisms that regulate the cell cycle entry and exit, and the division potential of NBs during development. During the course of our work on genetic regulation of asymmetric division of precursors, we isolated a mutation that caused additional divisions of precursor cells in many lineages in the nerve cord. We cloned the gene and found that it is a member of the T-box protein family. These proteins play important roles from development to cancer. Our studies on this gene, midline, led us to believe that it regulates precursor cell entry and exit from the cell-cycle. It appears to also play a role as part of a mechanism by partnering with Prospero. Thus, our specific aims are: 1) Determine the role of Mid in the cell cycle entry and exit by neuronal stem cells, 2) Determine the regulation of mid-expression, whether it is linked to the system that it regulates or originates outside of the cells it regulates, and 3) Determine if Mid partners with Prospero to specify the division potential of precursor cells. The cell cycle entry and exit by precursors and the regulation of their division potential are exceedingly difficult problems to study. Whether these regulatory mechanisms reside within the cell or extrinsic to cells, do cells measure the time elapsed, or is there a counting mechanism that determines/interacts with the cell cycle machinery, are all unknowns. Our aims are focused on exploring these issues using a powerful genetic system. By no means is this proposal only Mid or Pros-centric, these players are entry points to tackle the above problems in biology.

摘要

项目成果

Nuclear Prospero allows one-division potential to neural precursors and post-mitotic status to neurons via opposite regulation of Cyclin E.

• DOI: 10.1371/journal.pgen.1010339
• 发表时间: 2022-08
• 期刊: PLoS genetics
• 影响因子: 4.5

Restriction on self-renewing asymmetric division is coupled to terminal asymmetric division in the Drosophila CNS.

• DOI: 10.1371/journal.pgen.1009011
• 发表时间: 2020-09
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Gaziova I;Gazi M;Mar J;Bhat KM
• 通讯作者: Bhat KM

Preference and detrimental effects of high fat, sugar, and salt diet in wild-caught Drosophila simulans are reversed by flight exercise.

• DOI: 10.1096/fba.2020-00079
• 发表时间: 2021-01
• 期刊: FASEB bioAdvances
• 影响因子: 2.7
• 作者: Murashov AK;Pak ES;Lin CT;Boykov IN;Buddo KA;Mar J;Bhat KM;Neufer PD
• 通讯作者: Neufer PD