前神经基因Mash1 (Ascl1) 在多个基因系中表达,并调节它们的分化和特异化
1Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan. kameda@med.kitasato-u.ac.jp.
Histochemistry and cell biology
|August 26, 2025
概括
转录因子Ascl1 (也称为Mash1) 对于神经系统和神经内分泌细胞的发展至关重要. 它的缺失导致这些关键细胞类型的严重发育缺陷.
科学领域:
- 发育生物学
- 神经科学
- 细胞生物学
背景情况:
- Ascl1 (Mash1) 是bHLH转录因子,对神经元前体的发育至关重要.
- 它调节来自神经细胞的自主神经系统 (交感性,副交感性,肠道) 的分化.
- Ascl1还控制各种器官的神经内分泌细胞的分化,包括带体,上腺髓,甲状腺C细胞和肺神经上皮体.
研究的目的:
- 研究Ascl1在神经元和神经内分泌细胞系的发展和分化中的重要作用.
- 了解Ascl1缺乏对特定细胞类型和组织的形成的影响.
- 确定影响Ascl1表达的调节因素.
主要方法:
- 分析Ascl1-null突变小鼠以观察发育缺陷.
- 检查分化标志物,包括甲醇胺和血清的表达.
- 研究Phox2b和Hes1基因对Ascl1表达的调控作用.
主要成果:
- Ascl1-null突变体表现出自主性和各种神经内分泌细胞的缺陷发育和分化.
- 在缺乏Ascl1的模型中,嗅觉上皮和球泡的发育受损.
- 中枢神经系统的区域,如弧形核,中腹脑部,心脏部和单独的核道显示消除或缩.
- 受影响的细胞和组织始终表达甲基胺和/或血清素.
- Phox2b作为转录激活剂,而Hes1则作为Ascl1表达的抑制剂.
结论:
- Ascl1对于广泛的神经和神经内分泌细胞类型的适当发育和分化是不可或缺的.
- 它的功能扩展到外周和中枢神经系统,以及来自不同胚胎的神经内分泌衍生物.
- Ascl1表达受到Phox2b和Hes1等上游因素的严格调节,突出显示了复杂的调节网络.
相关概念视频
01:51Determination
19.1K
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...
19.1K
01:30Neurulation
42.6K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
42.6K
02:24Regulation of Expression Occurs at Multiple Steps
3.1K
3.1K
01:23Regulation of Expression at Multiple Steps
996
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
996
03:14Notch Signaling Pathway
4.4K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.4K
02:02Cis-regulatory Sequences
10.1K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
10.1K