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《Developmental neurobiology》2017,77(10):1206-1220
Adult neurogenesis occurs more commonly in teleosts, represented by zebrafish, than in mammals. Zebrafish is therefore considered a suitable model to study adult neurogenesis, for which the regulatory molecular mechanisms remain little known. Our previous study revealed that neuroepithelial‐like neural stem cells (NSCs) are located at the edge of the dorsomedial region. We also showed that Notch signaling inhibits NSC proliferation in this region. In the present study, we reported the expression of Wnt and Shh signaling components in this region of the optic tectum. Moreover, inhibitors of Wnt and Shh signaling suppressed NSC proliferation, suggesting that these pathways promote NSC proliferation. Shh is particularly required for maintaining Sox2‐positive NSCs. Our experimental data also indicate the involvement of these signaling pathways in neural differentiation from NSCs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1206–1220, 2017  相似文献   

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Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.  相似文献   

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不对称分裂是干/祖细胞发育分化中的基本过程,膜相关蛋白Numb在其中发挥重要作用.Numb极性分布于细胞一侧,在干/祖细胞有丝分裂时不对等分配至两个子代细胞,使子代细胞产生不同分化命运.如一个保持在干/祖细胞状态,而另一个发育为神经元,这一过程主要通过抑制Notch信号通路发挥作用.近年在哺乳动物中的研究中发现,高强度Notch信号又能够反馈抑制Numb活性.Numb具有维持神经干/祖细胞增殖与促进分化的双重作用,Numb的命运决定作用还与Shh信号通路和p53蛋白等相关.另外,Numb参与调控细胞的粘连、迁移以及神经元轴突的分支与延长.本文主要对Numb在果蝇及哺乳动物神经干/祖细胞中的定位以及其在决定细胞命运和分化中的调控作用进行综述.  相似文献   

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Both embryonic and adult neurogenesis involves the self-renewal/proliferation,survival,migration and lineage differentiation of neural stem/progenitor cells.Such dynamic process is tightly regulated by...  相似文献   

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Multiple signaling pathways regulate proliferation and differentiation of neural progenitor cells during early development of the central nervous system (CNS). In the spinal cord, dorsal signaling by bone morphogenic protein (BMP) acts primarily as a patterning signal, while canonical Wnt signaling promotes cell cycle progression in stem and progenitor cells. However, overexpression of Wnt factors or, as shown here, stabilization of the Wnt signaling component beta-catenin has a more prominent effect in the ventral than in the dorsal spinal cord, revealing local differences in signal interpretation. Intriguingly, Wnt signaling is associated with BMP signal activation in the dorsal spinal cord. This points to a spatially restricted interaction between these pathways. Indeed, BMP counteracts proliferation promoted by Wnt in spinal cord neuroepithelial cells. Conversely, Wnt antagonizes BMP-dependent neuronal differentiation. Thus, a mutually inhibitory crosstalk between Wnt and BMP signaling controls the balance between proliferation and differentiation. A model emerges in which dorsal Wnt/BMP signal integration links growth and patterning, thereby maintaining undifferentiated and slow-cycling neural progenitors that form the dorsal confines of the developing spinal cord.  相似文献   

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Notch and gp130 signaling are involved in the regulation of multiple cellular processes across various tissues during animal ontogenesis. In the developing nervous system, both signaling pathways intervene at many stages to determine cell fate—from the first neural lineage commitment and generation of neuronal precursors, to the terminal specification of cells as neurons and glia. In most cases, the effects of Notch and gp130 signaling in these processes are similar. The aim of the current review was to summarize the knowledge regarding the roles of Notch and gp130 signaling in the maintenance of neural stem and progenitor cells during animal ontogenesis, from early embryo to adult. Recent data show a direct crosstalk between these signaling pathways that seems to be specific for a particular type of neural progenitors.  相似文献   

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Notch和Wnt信号通路能够调控细胞的分化、增殖、迁移和粘附等多种行为,在胚胎发育、干细胞分化及肿瘤生长等方面发挥多样性的调控作用.血管形成过程中的典型事件包括尖端细胞(tipcell)和柄细胞(stalkcell)分化、柄细胞增殖、内皮细胞迁移和粘附、血管重塑以及动静脉分化等.本文对Notch和Wnt信号通路在血管形成不同阶段的功能作一综述,以期描述Notch和Wnt是怎样在分子水平上协同作用进而调控血管的形成.从两条信号通路的分子水平及复杂信号网络中众多成员协调作用的角度了解血管形成的机制,对于调整肿瘤等涉及血管形成的相关疾病的治疗策略具有一定意义.  相似文献   

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小肠上皮具有快速更新的能力,是研究成体干细胞的理想系统.小肠上皮由绒毛和隐窝两部分组成,而位于小肠隐窝底部的小肠干细胞是其持续更新的源泉.近年来,以Lgr5为代表的小肠干细胞标记物的发现、Lgr5+小肠干细胞的分离培养和多种转基因小鼠模型的出现,极大地促进了对小肠干细胞自我更新和分化调控的研究,使得人们可以更加深入地认识小肠干细胞命运决定的分子机制.本文简要综述了近年来人们对Wnt,BMP,Notch和EGF等信号如何在小肠干细胞命运调控中发挥作用的认识.  相似文献   

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Breast cancer angiogenesis is elicited and regulated by a number of factors including the Notch signaling. Notch receptors and ligands are expressed in breast cancer cells as well as in the stromal compartment and have been implicated in carcinogenesis. Signals exchanged between neighboring cells through the Notch pathway can amplify and consolidate molecular differences, which eventually dictate cell fates. Notch signaling and its crosstalk with many signaling pathways play an important role in breast cancer cell growth, migration, invasion, metastasis and angiogenesis, as well as cancer stem cell (CSC) self-renewal. Therefore, significant attention has been paid in recent years toward the development of clinically useful antagonists of Notch signaling. Better understanding of the structure, function and regulation of Notch intracellular signaling pathways, as well as its complex crosstalk with other oncogenic signals in breast cancer cells will be essential to ensure rational design and application of new combinatory therapeutic strategies. Novel opportunities have emerged from the discovery of Notch crosstalk with inflammatory and angiogenic cytokines and their links to CSCs. Combinatory treatments with drugs designed to prevent Notch oncogenic signal crosstalk may be advantageous over λ secretase inhibitors (GSIs) alone. In this review, we focus on the more recent advancements in our knowledge of aberrant Notch signaling contributing to breast cancer angiogenesis, as well as its crosstalk with other factors contributing to angiogenesis and CSCs.  相似文献   

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Nemeth MJ  Bodine DM 《Cell research》2007,17(9):746-758
Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal (in which the ability to function as HSCs is retained) and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the "niche", focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.  相似文献   

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All blood cells are derived from multipotent stem cells, the so-called hematopoietic stem cells (HSCs), that in adults reside in the bone marrow. Most types of blood cells also develop there, with the notable exception of T lymphocytes that develop in the thymus. For both HSCs and developing T cells, interactions with the surrounding microenvironment are critical in regulating maintenance, differentiation, apoptosis, and proliferation. Such specialized regulatory microenvironments are referred to as niches and provide both soluble factors as well as cell-cell interactions between niche component cells and blood cells. Two pathways that are critical for early T cell development in the thymic niche are Wnt and Notch signaling. These signals also play important but controversial roles in the HSC niche. Here, we review the differences and similarities between the thymic and hematopoietic niches, with particular focus on Wnt and Notch signals, as well as the latest insights into regulation of these developmentally important pathways.  相似文献   

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