在早期大脑发育过程中,Tet通过谷氨基基质信号传递来控制轴突指导
Hiep Tran1, Le Le1, Badri Nath Singh1
1Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA.
iScience
|April 24, 2024
概括
十一转位 (TET) 蛋白调节大脑发育. TET蛋白通过调节Drosophila中的谷氨基信号传递来控制体轴突指导,影响神经发育障碍.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 十一转位 (TET) 蛋白中的突变与人类神经发育障碍有关.
- TET蛋白在细胞过程中起着至关重要的作用,但它们在早期大脑发育中的功能尚未完全理解.
研究的目的:
- 为了研究Tet在Drosophila早期大脑发育中的作用.
- 阐明Tet影响轴突指导和神经发育的分子机制.
主要方法:
- 使用Drosophila melanogaster作为一个模型生物.
- 研究了体 (MB) 轴突指导中的Tet DNA结合域的功能.
- 分析了胺合成酶2 (Gs2) 在Tet突变大脑中的表达.
- 研究了操纵Gs2水平和谷氨酸酸信号对MB轴突指导的影响.
- 评估了Tet和Drosophila Fmr1.1之间的遗传相互作用.
主要成果:
- 泰特DNA结合域对于Drosophila的MB轴突引导至关重要.
- 谷氨酸合成酶2 (Gs2) 在Tet突变大脑中显著下调,其损失使得Tet表型重现.
- 在胰岛素生成细胞 (IPC) 中,Tet和Gs2的功能是调节MB轴突导向.
- 在IPC中过度表达Gs2拯救了Tet突变表型.
- 调节谷氨基基信号传递 (使用MPEP或谷氨基酸) 影响Tet突变表型.
- 泰特和多索菲拉Fmr1突变体具有相似的发育缺陷,Gs2过度表达拯救了Fmr1表型.
结论:
- 泰特蛋白是多索菲拉幼虫早期大脑发育的关键调节者.
- 控制MB轴突指导通过调节Gs2涉及的Glutamatergic信号传递,并在IPC中起作用.
- 这些发现提供了与TET突变相关的神经发育障碍的分子基础的见解.
相关概念视频
Neurulation
40.2K
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...
40.2K
Microtubule Formation
6.3K
Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
6.3K
Assembly of Complex Microtubule Structures
2.1K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
2.1K
Microtubules in Signaling
1.5K
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
1.5K
Non-Canonical Wnt Signaling Pathways
6.4K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
6.4K
Activation and Inactivation of G Proteins
8.9K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
8.9K


