哺乳动物早期胚胎细胞的极性与分化

哺乳动物早期胚胎细胞具有极性,在桑椹胚以前细胞极性由不稳定变为稳定。细胞极性包括表面极性和细胞质极性。细胞极性与滋养层和内细胞团两种细胞系的建立密切相关。细胞的极化使细胞形成顶-基轴,细胞分裂后,顶半球产生的极性子细胞分化为滋养层,基半球产生的非极性子细胞建立了内细胞团。内细胞团偏向胚泡一侧,使胚胎形成了胚-对胚轴(EA轴)。细胞分化是许多因素的综合效应,不能简单地归结为决定子的单独作用。     

RHO蛋白家族与细胞极性

细胞的极性形成对细胞发育、分化及其功能的发挥起着举足轻重的作用,细胞极性的丧失与肿瘤的发生发展密切相关.小G蛋白Rho家族是肌动蛋白细胞骨架重新组装的主要调节因子之一,在协调细胞极性化和正常的形态形成过程中起重要作用.现就Rho蛋白家族与细胞极性及二者的关系作一综述.     

DNA与个体发育调控(2)

生物结构的形成需要各种细胞按照类型分别聚集,这主要是通过细胞表面的钙黏蛋白实现的。形成片、管、腔等结构需要细胞具有极性;上皮表面上的的结构如纤毛、羽毛、鳞片、毛发具有方向性,也需要有关细胞具有极性。细胞的极性是由细胞内和细胞表面的一些蛋白质聚合物彼此拮抗并不对称分布而形成的。细胞之间通过Notch蛋白及其配体之间的相互作用导致彼此相邻的细胞向不同的分化方向发展。这些"成型分子"在胚胎发育过程中都发挥重要的作用。     

用实验方法反转原肠胚外胚层细胞的极性(英文)

过去的工作指出,在紧密连接形成的时候,紧密连接本身也经历了极性化的过程,而且这一过程在时间上和囊胚腔的出现和扩张是相互关连的。为了进一步探讨紧密连接的极性化和外胚层细胞极性之间的关系,进行了原肠胚外胚层细胞内外反转的实验,结合扫描和透射电镜的观察,指出反转后的外胚层细胞表面发生了明显的变化,在原来没有紧密连接的内层细胞的外缘形成了发育完善的紧密连接。内外反转的这一实验操作,使外胚层细胞和内外环境的关系发生了变化。很可能外胚层细胞的极性先发生了反转,然后影响紧密连接在新的向外的一极形成。     

被子植物的早期胚胎形态建成

被子植物早期胚胎形态建成是其有性生殖过程中一个重要发育阶段。在这一阶段中,被子植物形体基本特征形成,包括顶-基轴极性建立、不同细胞层分化以及分生组织形成。合子极性直接与顶基细胞命运相关,但其极性产生机理仍然不明。研究表明,WOX家族转录因子、生长素定向运输以及生长素响应应答可能参与了早期顶-基模型建成;辐射对称模型的建立可能由细胞与细胞间相互作用来介导;生长素流可能参与胚胎顶端组织形成。该文对近年来被子植物早期胚胎形态建成过程中的合子极性建立与生长、合子分裂及其顶基细胞的形成、胚根原特化及根极的形成、辐射对称模式及表皮原特化、顶端分生组织特化及子叶起始等方面的研究进展进行了综述。     

非典型蛋白激酶C复合物在细胞极性建立中的作用

极性是多数细胞的共同特征,是细胞分化和细胞行使正常功能的基础,细胞极性的建立对于生物体的生长发育至关重要。过去十年的研究显示,进化上保守的非典型蛋白激酶C(aPKC)复合物在许多生物的多种细胞中都参与了细胞极性的建立,并且在其中扮演着相当重要的角色,这为揭示极性建立的机制提供了重要的线索。以线虫合子前-后极(anterior-posterior)的形成、哺乳动物和果蝇上皮细胞顶-底极(apical-basal)的建立以及果蝇神经母细胞不对称分裂中细胞命运决定子的分配这3个典型的极性过程为主线,综述了aPKC复合物在细胞极性建立中的作用,并探讨其中的分子机制。     

陈正军组关于上皮细胞极性建立机制的研究取得突破

2006年11月1日出版的EMBOJ发表了上海生科院生化与细胞所陈正军课题组关于EGFR信号通路调控上皮细胞极性建立的最新研究成果,该工作首次确定了生长因子受体与Src家族成员协同介导重要极性蛋白Par3磷酸化直接调控上皮细胞极性建立的分子机理,从而首次揭示了一种新的酪氨酸磷酸化依赖性的上皮细胞极性形成的调控机制。细胞极性对多细胞有机体的发育是至关重要的,而上皮细胞极性的建立与维持对于各器官正常功能的运转是必不可少的。由Par3、Par6和aPKC组成的保守复合物是各种细胞极性建立以及细胞不对称分裂的核心部件。尽管对该复合物…     

细胞不对称分裂

细胞不对称分裂是多细胞生物发育的基础。细胞不对称分裂的重要特征是细胞命运决定子在细胞分裂期间的不对称分离。细胞不对称分裂一般要经历4个步骤：在细胞中建立一个极性轴;沿此轴定向并形成纺锤体;细胞命运决定子沿极性轴作极性分布;细胞分裂后,不同的细胞命运决定子指导决定细胞的不同命运。     

MCF-7细胞在亚多层中细胞膜极性的变化

人乳腺癌细胞株MCF-7细胞于微孔滤膜上经较长时间培养后形成亚多层。表层细胞保持了单层MCF-7细胞所具有的形态学极性与膜极性特征。免疫酶细胞化学技术显示,97.5%的细胞表达了表面乳脂球膜抗原MAM-6,并且该抗原呈顶面极性分布。深层细胞没有面向培养液的游离面,缺乏形态学极性特征,仅??12.9%的细胞表达表面MAM-6,且呈无极性随机分布。深层细胞胞质的MAM-6免疫染色强度大于表层细胞。本研究结果提示,非对称性空间环境(由液相空间与固相空间构成)对于MCF-7细胞的膜极性的建立是必需的。     

内皮屏障与极性运输

极化细胞的极性分布和功能行使,需要不同机制相互协作,改变胞内蛋白的运输和分布,并对环境变化做出极性应激。内皮细胞(endothelial cells,ECs)是一类具有极性特征的单层特化上皮细胞,在结构和功能上形成面向血液的顶端区域(apical membrane domain)和面向下方平滑肌细胞的基底侧区域(basolateral membrane domain)。内皮功能障碍和细胞极性丢失,与心血管疾病及癌症的发生紧密相关。在炎症和免疫应答中,内皮细胞通过胞内蛋白的持续分选维持极性,协助血液中大分子跨过内皮屏障完成生理功能,同时,对血液或组织中的生理变化做出极性应答。     

Polarized Organization of the Cytoskeleton: Regulation by Cell Polarity Proteins

Polarity is one of the fundamental properties displayed by living organisms. In metazoans, cell polarity governs developmental processes and plays an essential role during maintenance of forms of tissues as well as their functions. The mechanisms of establishment and maintenance of cell polarity have been investigated extensively in the last two decades. This has resulted in identification of “core cell polarity modules” that control anterior–posterior, front–rear and apical–basal polarity across various cell types. Here, we review how these polarity modules interact closely with the cytoskeleton during establishment and maintenance of cytoskeletal polarity. We further suggest that reciprocal interactions between cell polarity modules and the cytoskeleton consolidate the initial weaker polarity, arising from an external cue, into a committed polarized system.     

Cell polarity, auxin transport, and cytoskeleton-mediated division planes: who comes first?

In plants, cell polarity is an issue more recurring than in other systems, because plants, due to their adaptive and flexible development, often change cell polarity postembryonically according to intrinsic cues and demands of the environment. Recent findings on the directional movement of the plant signalling molecule auxin provide a unique connection between individual cell polarity and the establishment of polarity at the tissue, organ, and whole-plant levels. Decisions about the subcellular polar targeting of PIN auxin transport components determine the direction of auxin flow between cells and consequently mediate multiple developmental events. In addition, mutations or chemical interference with PIN-based auxin transport result in abnormal cell divisions. Thus, the complicated links between cell polarity establishment, auxin transport, cytoskeleton, and oriented cell divisions now begin to emerge. Here we review the available literature on the issues of cell polarity in both plants and animals to extend our understanding on the generation, maintenance, and transmission of cell polarity in plants.     

Tiam1 takes PARt in cell polarity

Cell polarity is an essential requirement for the proper tissue development of complex organisms. This is underscored by in vivo studies showing that loss of cell polarity contributes to the formation and progression of tumours. Evolutionary conserved multiprotein complexes, such as the Par3-Par6-aPKC or, in short, the Par polarity complex, regulate the establishment of cell polarity. The small Rho GTPases CDC42 and Rac control the activation of the Par polarity complex. Evidence now implicates the Rac activator Tiam1 as a crucial component of the Par complex in regulating neuronal (axonal) and epithelial (apical-basal) polarity. Our current knowledge places Tiam1 at the centre of a pivotal biological process, the establishment and maintenance of cell polarity, and suggests that deregulation of the Tiam1-Par complex contributes to tumourigenicity.     

Cyclin E-Cdk2 temporally regulates centrosome assembly and establishment of polarity in Caenorhabditis elegans embryos

Establishment of polarity in C. elegans embryos is dependent on the centrosome. The sperm contributes a pair of centrioles to the egg and these centrioles remain incapable of polarizing the cortex while the egg completes meiosis. Coincident with the establishment of polarity, the centrioles recruit centrosomal proteins, several of which are required for polarity, suggesting that the temporal regulation of centrosome assembly may control the initiation of polarization. We found that cyclin E-Cdk2 is required for the establishment of polarity. Cyclin E-Cdk2 controls the recruitment of centrosomal proteins specifically at the time of polarity establishment. Cyclin E is required for several examples of asymmetric cell division and fate determination in C. elegans and Drosophila. Here, we suggest a possible mechanism for cyclin E-Cdk2-dependent differentiation: the establishment of cortical polarity by the centrosome.     

Notochord morphogenesis: a prickly subject for ascidians

Orchestrated cell movements marshalled by proper cell polarity in the developing body axes are fundamental to the elongation of the notochord during chordate embryogenesis. A recent study shows that, in ascidians, the planar cell polarity gene prickle regulates sequential establishment of cell polarity during two phases of notochord morphogenesis.     

Centrosomes can initiate a polarity axis from any position within one-cell C. elegans embryos

The stereotyped asymmetry of one-cell C. elegans embryos has proven to be an important model for identifying molecular determinants of cell polarity. How polarity is initiated is less well understood. Polarity establishment depends on centrosomes, which use two molecularly distinct pathways to break symmetry. In both, the centrosome's position adjacent to the cell cortex is thought to determine where polarization starts. Defects in centrosome-cortex juxtaposition correlate with defects in polarity establishment in several mutants, suggesting that these processes may be linked, but there is no direct test of this. Here we assess how centrosome position relative to the cortex affects polarity establishment. We find that centrosomes can initiate polarity from any position within the embryo volume, but centrosome-cortex proximity decreases the time required to initiate polarity. Polarization itself brings about close centrosome-cortex proximity. Prior to polarization, cytoplasmic microtubules constrain centrosome movement near the cortex, expanding the controversial role of microtubules during polarity establishment. The ability of centrosomes to induce a single polarity axis from any position within the egg emphasizes the flexible, self-organizing properties of polarization in C. elegans embryos and contrasts the common view of C. elegans development as invariant.     

Robust polarity establishment occurs via an endocytosis-based cortical corralling mechanism

Formation of a stable polarity axis underlies numerous biological processes. Here, using high-resolution imaging and complementary mathematical modeling we find that cell polarity can be established via the spatial coordination of opposing membrane trafficking activities: endocytosis and exocytosis. During polarity establishment in budding yeast, these antagonistic processes become apposed. Endocytic vesicles corral a central exocytic zone, tightening it to a vertex that establishes the polarity axis for the ensuing cell cycle. Concomitantly, the endocytic system reaches an equilibrium where internalization events occur at a constant frequency. Endocytic mutants that failed to initiate periodic internalization events within the corral displayed wide, unstable polarity axes. These results, predicted by in silico modeling and verified by high resolution in vivo studies, identify a requirement for endocytic corralling during robust polarity establishment.     

Protein Complex Assemblies in Epithelial Cell Polarity and Asymmetric Cell Division

Asymmetric local concentration of protein complexes on distinct membrane regions is a fundamental property in numerous biological processes and is a hallmark of cell polarity. Evolutionarily conserved core polarity proteins form specific and dynamic networks to regulate the establishment and maintenance of cell polarity, as well as distinct polarity-driven cellular events. This review focuses on the molecular and structural basis governing regulated formation of several sets of core cell polarity regulatory complexes, as well as their functions in epithelial cell polarization and asymmetric cell division.     

Budding and cell polarity in Saccharomyces cerevisiae.

Budding by yeast follows a sequence of three stages. These include selection of a non-random bud-site, organization of that site and establishment of an associated axis of cytoskeletal polarity, and localized growth of the cell surface to produce the bud. Numerous components involved in each stage have been identified. As some of these components have close homologs in other organisms, there may exist common mechanisms involved in the establishment of cell polarity.     

Cell polarity: a new mod(e) of anchoring

Microtubules play a central role in the establishment of cell polarity by directing the transport of polarity determinants to their site of action. Recent work has revealed a novel membrane-anchoring mechanism which complements the microtubule transport of the fission yeast polarity determinant tea1p to ensure its retention at the cell tip.