通过持续的转录因子对神经元分化和连接进行协调控制
Mehmet Neset Özel1, Claudia Skok Gibbs2,3, Isabel Holguera1
1Department of Biology, New York University, New York, NY 10003, USA.
Science (New York, N.Y.)
|December 8, 2022
概括
科学家发现转录因子定义了Drosophila视觉系统中的不同类型的神经元. 修改这种遗传密码可预见地改变神经元命运, 提供了一个理解大脑细胞类型规范的框架.
科学领域:
- 神经科学
- 发育生物学
- 遗传学
背景情况:
- 神经系统中神经细胞类型的巨大多样性对理解细胞命运的遗传基础构成了重大挑战.
- 确定确定不同神经元身份的精确分子机制对于理解大脑发育和功能至关重要.
研究的目的:
- 研究转录因子在复杂Drosophila视觉系统中的神经元命运中的作用.
- 建立一个框架来理解转录因子的连续表达如何定义单个神经元类型以及如何操纵这个代码.
主要方法:
- 使用Drosophila视觉系统作为模型生物.
- 采用转录组分析来识别定义不同神经元的持续表达的转录因子.
- 进行转录因子组合的向基因改造.
- 对开放的染色体区域进行了 cis 调节分析.
- 开发并验证了基因调节的网络模型.
主要成果:
- 德洛索菲拉视觉系统中近200种不同的神经元类型的特征是大约10个连续表达的转录因子的独特组合.
- 这种转录因子代码的有针对性的改变导致神经元命运的可预测和完整转换,通过形态和转录分析得到证实.
- 基因调控分析将一个关键基因与干细胞命运规范中的上游模式因素联系起来.
- 经过验证的网络模型阐明了终端选择器和ecdysone信号在神经连接期间调节基因表达中的协同作用.
结论:
- 已经建立了一个可概括的框架,说明特定的神经元命运如何在转移后的神经元中实现.
- 这项研究表明,转录因子的组合表达作为"终端选择码"来建立和维持神经元的身份.
- 研究结果提供了关于神经元多样性和大脑连接的发展机制的见解.
更多相关视频
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
7.6K
09:07Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
Published on: March 17, 2014
13.8K
相关概念视频
02:23Master Transcription Regulators
7.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K
02:33Combinatorial Gene Control
8.4K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.4K
01:51Determination
18.9K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
18.9K
01:29Somatic to iPS Cell Reprogramming
2.3K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.3K
01:30General Transcription Factors
5.5K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.5K
01:10Transcription
147.6K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
147.6K