用POU域因子对皮层神经元迁移的转录调节
Robert J McEvilly1, Marcela Ortiz de Diaz, Marcus D Schonemann
1Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0648, USA.
Science (New York, N.Y.)
|February 23, 2002
概括
转录因子Brn-1和Brn-2通过控制神经元迁移来调节皮层发育. 它们的缺失导致大脑结构的严重缺陷,特别是小鼠的皮质逆转.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 哺乳动物大脑皮层的适当分层对于认知功能至关重要.
- 众所周知,激酶Cdk5和连接物reelin介导皮质发育途径.
- 了解皮层发育的分子机制是一个正在进行的研究领域.
研究的目的:
- 为了确定Cdk5-介导的皮质层层的关键调节者.
- 研究III类POU域转录因子Brn-1和Brn-2在前脑发育中的作用.
- 阐明 Brn-1 和 Brn-2 控制神经元迁移和皮层发育的分子机制.
主要方法:
- 在小鼠模型中对Brn-1和Brn-2功能的遗传分析.
- 对Cdk5调控子单元 (p35和p39) 的基因表达的分析.
- 在野生类型和淘汰赛小鼠中检查皮质层层和神经元迁移.
主要成果:
- Brn-1和Brn-2在大多数II-V层皮质神经元中共同表达.
- Brn-1和Brn-2在迁移神经元中冗余调节p35和p39的细胞自主表达.
- Brn-1(-/-) /Brn-2(-/-) 小鼠表现出一种严重的皮质形,称为皮质逆转.
- 这些转录因子在皮层发育期间关键控制辐射迁移的启动.
结论:
- Brn-1和Brn-2是Cdk5介导的皮质层层的重要调节者.
- 这些因素在启动皮层神经元的辐射迁移方面发挥着关键的,冗余的作用.
- 干扰Brn-1和Brn-2功能导致大脑皮层发育的严重缺陷.
相关概念视频
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
02:33Combinatorial Gene Control
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...
02:23Master Transcription Regulators
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...
02:23Master Transcription Regulators
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...
01:23Propagation of Action Potentials
The propagation of an action potential refers to the process by which a nerve impulse, or "action potential," travels along a neuron.
Neurons (nerve cells) have a resting membrane potential, with a slightly negative charge inside compared to outside. This is maintained by ion channels, such as sodium (Na+) and potassium (K+) channels, which control the flow of ions. When a stimulus, like a touch or a signal from another neuron, triggers the neuron, sodium channels open, allowing sodium ions to...
Neurons (nerve cells) have a resting membrane potential, with a slightly negative charge inside compared to outside. This is maintained by ion channels, such as sodium (Na+) and potassium (K+) channels, which control the flow of ions. When a stimulus, like a touch or a signal from another neuron, triggers the neuron, sodium channels open, allowing sodium ions to...
01:32Postsynaptic Potential (PSP)
Postsynaptic potential (PSP) refers to a change in the electrical potential of a neuron when neurotransmitters released by presynaptic neurons bind to postsynaptic receptors. This potential can either be excitatory, leading to depolarization and ultimately action potential generation, or inhibitory, leading to hyperpolarization and suppression of the postsynaptic neuron.
There are two types of receptors: ionotropic and metabotropic.
The ionotropic receptor is the membrane protein that has an...
There are two types of receptors: ionotropic and metabotropic.
The ionotropic receptor is the membrane protein that has an...