Wnt and EGF pathways act together to induce C. elegans male hook development

Comparative studies of vulva development between Caenorhabditis elegans and other nematode species have provided some insight into the evolution of patterning networks. However, molecular genetic details are available only in C. elegans and Pristionchus pacificus. To extend our knowledge on the evolution of patterning networks, we studied the C. elegans male hook competence group (HCG), an equivalence group that has similar developmental origins to the vulval precursor cells (VPCs), which generate the vulva in the hermaphrodite. Similar to VPC fate specification, each HCG cell adopts one of three fates (1°, 2°, 3°), and 2° HCG fate specification is mediated by LIN-12/Notch. We show that 2° HCG specification depends on the presence of a cell with the 1° fate. We also provide evidence that Wnt signaling via the Frizzled-like Wnt receptor LIN-17 acts to specify the 1° and 2° HCG fate. A requirement for EGF signaling during 1° fate specification is seen only when LIN-17 activity is compromised. In addition, activation of the EGF pathway decreases dependence on LIN-17 and causes ectopic hook development. Our results suggest that WNT plays a more significant role than EGF signaling in specifying HCG fates, whereas in VPC specification EGF signaling is the major inductive signal. Nonetheless, the overall logic is similar in the VPCs and the HCG: EGF and/or WNT induce a 1° lineage, and LIN-12/NOTCH induces a 2° lineage. Wnt signaling is also required for execution of the 1° and 2° HCG lineages. lin-17 and bar-1/β-catenin are preferentially expressed in the presumptive 1° cell P11.p. The dynamic subcellular localization of BAR-1-GFP in P11.p is concordant with the timing of HCG fate determination.     

气孔发育及其调控

气孔是植物与外界环境进行气体交换的重要通道,对其密度与分布的调控影响着植物的生存与生长。最近的研究工作已经鉴定了一系列参与气孔发育调控的转录因子和信号肽,并对其调控机制有了初步的了解。本文综述了最近几年有关气孔发育方面的研究进展,总结了参与气孔发育的相关因子,并对进一步研究需要解决的问题进行了简要的探讨。     

Extending the family table: Insights from beyond vertebrates into the regulation of embryonic development by FGFs

Since the discovery of fibroblast growth factors (FGFs) much focus has been placed on elucidating the roles for each vertebrate FGF ligand, receptor, and regulating molecules in the context of vertebrate development, human disorders and cancer. Studies in human, mouse, frog, chick, and zebrafish have made great contributions to our understanding of the role of FGFs in specific processes. However, in recent years, as more genomes are sequenced, information is becoming available from many non‐vertebrate models and a more complete picture of the FGF superfamily as a whole is emerging. In some cases, less redundancy in these FGF signaling systems may allow for more mechanistic insights. Studies in sea anemones have highlighted how ancient FGF signaling is and helped provide insight into the evolution of the FGF gene family. Work in nematodes has shown that different splice forms can be used for functional specificity in invertebrate FGF signaling. Comparing FGFs between urochordates and vertebrates as well as between different insect species reveals important clues into the process of gene loss, duplication and subfunctionalization of FGFs throughout evolution. Finally, comparing all members of the FGF ligand superfamily reveals variability in many properties, which may point to a feature of FGFs as being highly adaptable with regards to protein structure and signaling mechanism. Further studies on FGF signaling outside of vertebrates is likely to continue to complement work in vertebrates by contributing additional insights to the FGF field and providing unexpected information that could be used for medical applications. Birth Defects Research (Part C) 90:214–227, 2010. © 2010 Wiley‐Liss, Inc.     

Calcium,a pivotal player in photodynamic therapy?

Photodynamic therapy combines three non-toxic components: light, oxygen and a photosensitizer to generate singlet oxygen and/or other ROS molecules in order to target destruction of cancer cells. The damage induced in the targeted cells can furthermore propagate to non-exposed bystander cells thereby exacerbating the damage. Ca²⁺ signaling is strongly intertwined with ROS signaling and both play crucial roles in cell death. In this review we aimed to review current knowledge on the role of Ca²⁺ and ROS signaling, their effect on cell-cell propagation via connexin-linked mechanisms and the outcome in terms of cell death. In general, photodynamic therapy results in an increased cytosolic Ca²⁺ concentration originating from Ca²⁺ entry or Ca²⁺ release from internal stores. While photodynamic therapy can certainly induce cell death, the outcome depends on the cell type and the photosensitizer used. Connexin channels propagating the Ca²⁺ signal, and presumably regenerating ROS at distance, may play a role in spreading the effect to neighboring non-exposed bystander cells. Given the various cell types and photosensitizers used, there is currently no unified signaling scheme to explain the role of Ca²⁺ and connexins in the responses following photodynamic therapy. This article is part of a Special Issue entitled: Calcium signaling in health, disease and therapy edited by Geert Bultynck and Jan Parys.     

Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila

The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway, regulate synaptic development in vertebrates and invertebrates. At the Drosophila larval neuromuscular junction (NMJ), the retrograde BMP pathway is a part of the machinery that controls NMJ expansion concurrent with larval growth. We sought to determine whether the conserved Hippo pathway, critical for proportional growth in other tissues, also functions in NMJ development. We found that neuronal loss of the serine‐threonine protein kinase Tao, a regulator of the Hippo signaling pathway, results in supernumerary boutons which contain a normal density of active zones. Tao is also required for proper synaptic function, as reduction of Tao results in NMJs with decreased evoked excitatory junctional potentials. Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. Instead, our experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. Taken together, these results support a role for Tao as a novel inhibitor of BMP signaling in motor neurons during synaptic development and function.     

钙信号在卵母细胞激活中的作用

钙信号是胞内主要的第二信使之一,发挥广泛的作用如细胞分裂、细胞凋亡等,对细胞的生命活动起着非常重要的作用。在精子和卵母细胞中,钙信号对精子获能、顶体反应、卵母细胞成熟、受精及卵裂等一系列复杂的过程有非常重要的影响。现就Ca2 在卵母细胞中的释放机制、信号转导途径、调控功能作一综述。     

磷脂酶D的细胞信号转导作用

磷脂酶D(PLD)是一类重要的跨膜信号转导酶类.分别由一个基因家族的不同成员编码.植物PLD的总体域结构相似,只是不同类型之间在某些单元上有重要差异.它们各具独特的生物化学特性.不同的PLD在不同的胁迫类型启动的特定的细胞过程中执行独特的细胞信号转导功能.PLD与其它磷脂酶及Ca2 信使之间有交互作用,形成复杂的信号转导网络.这一网络在不同植物种类、器官、组织和细胞类型中表现出特异性.文章最后讨论了PLD研究中有待揭示的问题并展望了今后的发展方向.     

斑马鱼胚胎背腹轴建立的分子机制

脊椎动物胚胎发育起始于体轴的建立,是胚胎早期发育过程中最重要的事件之一。Wnt、BMP、Nodal和FGF等多个信号通路协同调控细胞分化和细胞运动,促进胚胎胚层的形成和空间上的分离,调控胚胎背腹轴、前后轴和左右轴线的分化,为胚胎进一步发育勾勒出蓝图。本文主要综述斑马鱼胚胎背腹轴建立的分子机制,包括背部组织中心简介;母源Wnt/β-catenin信号调控背部组织中心形成的分子机制;BMP信号调控背腹轴建立的分子机制。     

Cellular signaling and biological functions of R-spondins

R-spondins (RSPOs) are a family of cysteine-rich secreted proteins containing a single thrombospondin type I repeat (TSR) domain. A vast amount of information regarding cellular signaling and biological functions of RSPOs has emerged over the last several years, especially with respect to their roles in the activation of the WNT signaling pathway. The identification of several classes of RSPO receptors may indicate that this family of proteins can affect several signaling cascades. Herein, we summarize the current understanding of RSPO signaling and its biological functions, and discuss its potential therapeutic implications to human diseases.     

RAS蛋白在有丝分裂信号转导中的作用

致癌基因ｒａｓ编码的ＲＡＳ蛋白参与了多种细胞因子调控的有丝分裂过程。抗ＲＡＳ抗体能抑制细胞正常的有丝分裂。ｒａｓ基因转化的成纤维细胞ＮＩＨ３Ｔ３还具有在无血清和生长因子刺激下自发完成细胞周期的能力。在这种细胞中有活性氧的生成,抗氧化剂能抑制该细胞的有丝分裂。ＲＡＳ蛋白在有丝分裂的信号转导中参与了多条途径,是信号转导的重要组织者     

Classification of the Genes Involved in the Two-Component System of the Moss Physcomitrella patens

Physcomitrella patens, belonging to bryopsida, is a basal lineage of land plants. To gain insight into the diversification of the two-component system (TCS), which is widely conserved from prokaryotes to eukaryotes, we compiled TCS-associated genes by employing P. patens genome databases. The moss has a set of His-kinases (HKs), including homologs of the cytokinin- and ethylene-receptors in seed plants. In addition, it has a number of coding-sequences specifying unique HKs. We found evidence that a putative cytokinin-receptor HK in P. patans serves as a sensor for this hormone, and that the HK activity of a putative ethylene-receptor homolog is regulated by ethylene, as observed for Arabidopsis thaliana.     

The activin signaling pathway promotes differentiation of dI3 interneurons in the spinal neural tube

The generation of the appropriate types and numbers of mature neurons during the development of the spinal cord requires the careful coordination of patterning, proliferation, and differentiation. In the dorsal neural tube, this coordination is achieved by the combined action of multiple ligands of both the Wnt and TGF-beta families, and their effectors, such as the bHLH proteins. TGF-beta signaling acting through the BMP receptors is necessary for the generation of several dorsal interneuron types. Other TGF-beta ligands expressed in the dorsal neural tube interact with the Activin receptors, which signal via a different set of SMAD proteins than BMPs. The effects of Activin signaling on the developing neural tube have not been described. Here we have activated the Activin signal transduction pathway in a cell-autonomous manner in the developing chick neural tube. We find that a constitutively active Activin receptor promotes differentiation throughout the neural tube. Although most differentiated cell populations are unaffected by Activin signaling, the number of dorsal interneuron 3 (dI3) cells is specifically increased. Our data suggest that Activin signaling may promote the formation of the dI3 precursor cells within a region circumscribed by BMP signaling and that this function is not dependent upon BMP signaling.     

Mutations in SNF1 complex genes affect yeast cell wall strength

The trimeric SNF1 complex from Saccharomyces cerevisiae, a homolog of mammalian AMP-activated kinase, has been primarily implicated in signaling for the utilization of alternative carbon sources to glucose. We here find that snf1 deletion mutants are hypersensitive to different cell wall stresses, such as the presence of Calcofluor white, Congo red, Zymolyase or the glucan synthase inhibitor Caspofungin in the growth medium. They also have a thinner cell wall. Caspofungin treatment triggers the phosphorylation of the catalytic Snf1 kinase subunit at Thr210 and removal of this phosphorylation site by mutagenesis (Snf1-T210A) abolishes the function of Snf1 in cell wall integrity. Deletion of the PFK1 gene encoding the α-subunit of the heterooctameric yeast phosphofructokinase suppresses the cell wall phenotypes of a snf1 deletion, which suggests a compensatory effect of central carbohydrate metabolism. Epistasis analyses with mutants in cell wall integrity (CWI) signaling confirm that the SNF1 complex and the CWI pathway independently affect yeast cell integrity.     

Notch和Wnt信号通路在血管形成中的协同调控作用

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.     

Tobacco pollen tubes as cellular models for ion dynamics: improved spatial and temporal resolution of extracellular flux and free cytosolic concentration of calcium and protons using pHluorin and YC3.1 CaMeleon

The presence of both calcium (Ca²⁺) and proton (H⁺) apical gradients is necessary for polarized cell elongation to occur in pollen tubes. So far, most of these studies have been carried out in lily pollen tubes, using chemical probes. Yet, lily is a refractory model for molecular genetics, with no easy protocol available for the construction of stable transgenic lines. Tobacco, however, is well suited for both transformation and cell biology, with sexual organs that are accessible, easy to handle and visualize. Pollen tubes are in an ideal size range for sub-cellular imaging analyses using modern microscopy techniques. Ion homeostasis in tobacco pollen tubes has not been precisely characterized so far. Here, we characterize the H⁺ and Ca²⁺ spatial and temporal patterns in tobacco pollen tubes by the use of two fluorescent genetic probes, pHluorin and the YC3.1 yellow CaMeleon, and direct measurement of extracellular flux by ion-sensitive vibrating probes. A distinct 0.4 pH unit acidic gradient was found to stretch from the tip up to 40 μm into the tube shank. This gradient intensity displayed 1–4 min period oscillations and is reduced in the non-growing phase of an oscillatory cycle. Furthermore, sub-membrane and sub-apical alkaline domains were detected. Extracellular H⁺ fluxes oscillated between 10 and 40 pmol cm⁻² s⁻¹. Fourier and continuous wavelet analyses showed tubes with one or two major oscillatory components in both extra and intracellular H⁺ oscillations. Cytosolic Ca²⁺ was imaged by confocal microscopy, showing a V-shaped 40 μm gradient extending from the tip, from 0.2 to 1.0 μM, which oscillates with a 1–4 min period, but with only one major oscillatory component. Extracellular Ca²⁺ fluxes oscillate in most pollen tubes, between 2 and 50 pmol cm⁻² min⁻¹ and, like in H⁺, with one or two major oscillatory peaks. A combination of confocal and widefield microscopy showed that H⁺ and Ca²⁺ displayed different patterns and shapes inside the cell, sometimes suggesting a structurally complementary role for these 2 second messengers in the growth process. These data suggest that fluxes at the apex of the pollen tube are directly responsible for establishment and maintenance of the gradient. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

植物钙感受器及其介导的逆境信号途径

钙信号是植物生长发育和逆境响应的重要调控因子, 是植物生理与逆境生物学研究领域中的热点之一。当植物细胞受到外界逆境刺激时, 其胞内会产生具有时空特异性的Ca2+信号变化, 这种变化首先被胞内钙感受器所感知并解码, 再由钙感受器互作蛋白将信号传递到下游, 从而激活下游早期响应基因的表达或相关离子通道的活性, 最终产生特异性逆境响应。植物细胞通过感知胞内钙信号的变化如何识别来自外界不同性质或不同强度的刺激, 是近几年植物生物学家所关注的科学问题。文章主要总结了近几年在植物钙感受器研究领域中的最新进展, 包括钙依赖蛋白激酶(CDPKs)、钙调素(CaMs)、类钙调素蛋白(CMLs)、类钙调磷酸酶B蛋白(CBLs)及其互作蛋白激酶(CIPKs)等的结构、功能及其介导的逆境信号途径, 并提供新的见解和展望。