肾脏发育中信号通路的调控作用

肾脏发育是一个复杂的过程,需要在输尿管芽细胞和基质细胞相互诱导下,引起细胞生长、增殖、分化,从而产生肾单位及各种管状结构,最终发育为成熟的肾脏。在肾脏发育过程中,GDNF/Ret、Wnt、BMP等一系列信号通路参与了发育的调控过程。这些信号通路在肾脏发育的不同阶段或不同位置发挥着重要的调控作用,并且通路之间存在相互的调控,从而形成了一个复杂而精细的调控网络,保证了肾脏的正常发育。文章概括了肾脏发育的过程,总结了肾脏发育过程中相关信号通路对肾脏发育的调控作用以及信号通路之间的相互调控。     

生物信息学分析及预测miR-17-92的分子调控网络

miR-17-92是一个高度保守的基因家簇,参与哺乳动物多个器官发育并与多种实体瘤的发生密切相关。运用多个在线数据库,发现了miR-17-92的上游转录因子及下游靶基因间的多个前馈和反馈环路。并对参与miR-17-92调控环路的基因进行功能聚类分析,进而绘制出miR-17-92的核心调控网络图。结果提示miR-17-92与其上游转录因子共调控的靶基因可能参与了生物体的细胞周期调控,迁移、凋亡、激素应答、免疫系统发育等多种生物学过程,KEGG pathway分析提示其还与多种肿瘤 信号通路密切相关。因此,对miR-17-92分子调控网络生物信息学的分析可以有助于理解其在细胞发育和肿瘤发生过程中的作用机制并为后续实验验证提供良好的指导。     

C类花器官特征基因AGAMOUS(AG)调控植物花分生组织维持与终止研究进展

花分生组织的维持与终止在植物花器官发生和世代交替起着至关重要的作用。成功的花分生组织决定能够确保植物正常的生殖发育和生命周期进程。诸多研究表明AGAMOUS(AG)基因作为花器官分化和开花决定的主效调节因子,能够协调花发育过程中多种细胞命运决定。然而,关于AG参与调控植物世代交替及花分生组织维持与终止的分子调控机制尚不清晰。综述了近年来AG基因参与调控植物花分生组织维持与终止的研究进展及现状,以期为深入研究植物花器官分化过程中干细胞的维持和终止,以及干细胞活动与其他发育过程之间的分子调控过程提供参考。     

经典WNT信号通路与哺乳动物肺器官发育

肺器官发育是上皮和问充质相互作用的过程,由多条信号通路共同调控。已知经典WNT信号通路对细胞的增殖、凋亡和分化起着重要的调控作用,在小鼠等模式生物上研究发现,它也参与了哺乳动物肺器官发育的调控过程。综述近年来经典WNT信号通路成员在哺乳动物肺器官发育过程中的表达变化、作用功能及表达异常可能诱发的肺部疾病,以期为研究经典WNT信号通路调控人类肺器官发育的分子机制及相关肺部疾病的诊治奠定基础。     

牦牛miR-383的靶基因预测及生物信息学分析

MicroRNAs (miRNAs)是一类非编码的小分子单链RNA,通过与靶基因的mRNA结合,抑制mRNA的翻译,参与多种生物学过程.本实验室前期通过高通量测序发现90日龄牦牛胚胎的背最长肌中miR-383的表达量显著高于成年牦牛.为探究miR-383在牦牛骨骼肌发育中的分子功能和机制,本研究对miR-383的靶基因进行预测,并进行生物信息学分析.通过TargetScan、miRDB和miRanda 3个软件预测了miR-383的靶基因,然后合并miRTarbase数据库中已被证实的靶基因作为基因集,分别用DAVID和KOBAS3.0在线软件对基因集进行功能注释(GO分析)和Pathway信号通路富集分析.结果 表明,牦牛miR-383序列在各物种间高度保守,靶基因功能富集于CD8阳性T细胞增殖的调控、核糖核蛋白复合物定位和负调控T细胞分化等生物学过程.信号通路分析发现靶基因的信号通路显著富集于PI3K-Ak、AMPK、FoxO和Focal adhesion等与肌肉发育相关的信号通路中.该研究结果将为miR-383功能及调控机制的深入研究提供参考依据,也为解析牦牛肌肉发育的分子机制提供新的研究方向.     

Tbx18通过下调EMT信号分子参与调控心脏发育

转录因子Tbx18(Tbx18)在小鼠胚胎心外膜上皮细胞表达并调控心外膜上皮细胞向心系细胞分化.上皮间充质转化(EMT)过程是器官发育和形成的重要机制.为阐述Tbx18通过调控下游EMT关键信号分子参与心外膜上皮细胞分化和心脏发育,本研究运用Tbx18-Cre/Rosa26R-EYFP双杂合基因敲入小鼠和免疫荧光共聚焦,证实Tbx18+心系细胞和EMT关键信号分子Snail1、Smad、Slug、Twist在发育后期胚鼠心外膜和心外膜下间充质发生共聚焦.同时还发现,Tbx18在胚鼠不同发育阶段的表达模式和Tbx18+心系细胞内上述EMT关键信号分子的表达模式相似.Tbx18和EMT关键信号分子在发育心脏存在相似的时空表达模式,因此,它们之间可能存在相互调控作用.运用Tbx18突变技术揭示了Tbx18突变型胚鼠心脏EMT关键信号分子表达水平均较野生型显著下调,直接证实了上述4个EMT信号分子是Tbx18的可能靶点.理解Tbx18参与心脏发育的下游靶点有助于改善成年心脏损伤后的再生修复.     

miRNA在调控皮肤和毛囊发育中的作用

表皮发生和毛囊的周期性再生涉及一系列基因的激活和沉默。近年来的研究表明, miRNA的表达谱在表皮和毛囊组织中存在组织特异性, 在毛囊周期性发育中存在阶段特异性。大量miRNA参与表皮和毛囊的发生, 色素的沉着以及毛囊的周期性发育过程, 不同类型细胞中的miRNA通过与信号通路和调控因子相互作用形成了一个全方位、多层次的网络调控系统。文章综述了miRNA调控表皮内稳态和毛囊周期性发育的一些研究 进展, 旨在丰富miRNA参与的基因调控网路的研究, 进而为人工调控miRNA进行疾病治疗和分子育种提供 帮助。     

EZH2在心脏与血管发育中的作用

Zeste基因增强子人类同源物2(enhancer of zeste homolog 2, EZH2)是多梳蛋白抑制复合物2(polycomb repressive complex 2, PRC2)的主要元件之一，利用组蛋白甲基化酶活性发挥经典作用，抑制靶基因的表达。此外，EZH2通过甲基化其他蛋白，作为蛋白支架分子募集转录相关分子介导转录激活，与lncRNA及miRNA相互作用等非经典途径调控各项生命活动，与干细胞分化和组织器官发育关系密切。EZH2及其功能相关分子在心脏发育、血管发生等过程中发挥着至关重要的作用。靶向敲除小鼠心脏Ezh2基因会影响心肌组织及内皮源性组织的正常发育，造成广泛性的心脏发育缺陷。EZH2参与调控正常组织和肿瘤组织的血管生成，维持新生血管完整性，并参与调控内皮间质化和内皮造血转化。本文探讨了EZH2在心脏和血管发生领域的影响效应、调控机制，及其与相关疾病的关系。     

植物HY5蛋白结构与功能的研究进展

HY5（LONG HYPOCOTYL 5）为光形态建成的正调控因子,是光调控植物发育的分子开关。在光诱导的基因表达中,HY5调控着植物基因组中上千基因的表达,它既可以单独调控相关基因的表达,也可以与其他调控因子一起共同调控相关基因的表达。HY5蛋白除了在光形态建成中起作用外,还在植物激素的信号传递过程中起着极其重要的作用,它整合了光信号传递和植物激素的信号传递。本综述简要介绍HY5蛋白的结构、生理功能及其分子机制等方面有关的进展。     

Wt1在心脏发育中的作用

Wt1最初被认为是一种抑癌基因,现在发现其在器官形成和病理生理过程中发挥作用,它不仅影响肾脏而且影响心脏的发育。心外膜细胞在经历了上皮-间充质细胞转化后成为心血管前体细胞,之后继续分化为心肌细胞、冠状动脉血管细胞等,该过程在心脏发育中起到重要作用,而Wt1调控了这一重要的转化过程。本综述主要阐述Wt1通过Wnt/β-catenin信号通路和维甲酸信号通路调控EMT,影响心脏发育的机制。充分理解Wt1调控EMT产生心血管前体细胞的过程与分子机制,对于研究正常心脏发育及心脏再生有很大帮助。     

Comparative proteomic analysis of kidney development-related proteins in the pig

The development of the kidney is a complex process that serves as a model organ system for understanding many basic developmental mechanisms, and the pig kidney provides a useful and relevant model of kidney development and function. However, the molecular cascades involved in kidney development during embryonic development in the pig have not been elucidated fully. To better understand the molecular events associated with kidney development, we evaluated changes in gene expression during kidney development (days E40, E70, and E93) and compared these expressions with adults using two-dimensional gel electrophoresis. The functionally regulated proteins were identified by comparing differentially expressed proteins in embryonic kidneys vs. adult kidney. In addition, a representative set of the proteins was subjected to liquid chromatography tandem mass spectrometry analysis. Furthermore, the identified proteins were categorized according to their biological processes and molecular functions. Interestingly, 10 of the 25 proteins identified were apoptosis and actin cytoskeleton-related proteins, such as GRP75, α-fetoprotein, ANXA2, ANXA4, DDAH2, DJ-1, SOD2, cofilin1, vil1, and calbindin1. Based on these results, the proteomic approach was applied to identify specific protein expression changes in kidney tissues during development, and the expressional changes of these embryonic kidney proteins were found to be closely associated with the regulation of kidney development.     

Mesonephric kidney--a stem cell factory?

Mesonephros is a vestige, transient renal organ that functions only during embryonic development. The anatomy, position and even cellular fate of the mesonephric kidney varies drastically among mammalian species. The origin of mesonephros from intermediate mesoderm and the dependence of its differentiation on the nephric or Wolffian duct have been well established. Commonly accepted is also the mesonephric origin of epididymal ducts of the male reproductive tract. Recently, upon the more profound understanding of the molecular mechanisms involved in the development of the permanent mammalian kidney, some light has been shed over the molecular events taking place during the mesonephric development as well. Because of the functional and structural similarities between the mesonephric and metanephric kidneys, it is not surprising that many molecules regulating metanephric development are also activated during mesonephric development. However, the multifunctional nature of mesonephros has been unexpected. First, it serves as an embryonic secretory organ, in some mammalian species more so than in others. It is thereafter removed by programmed cell death. Second, it is a source of multiple stem cells including somatic cells in the male gonad, vascular endothelial cells, and hematopoietic stem cells. Thus, mesonephros is a challenging model for studies on epithelial differentiation and organogenesis, regulation of apoptosis, sex determination and stem cell differentiation. In this review, we focus in the molecular and stem cell aspects in the differentiation of the mammalian mesonephros.     

Tubulo-interstitial fibrosis: an emerging major health problem

The incidence of chronic kidney disease leading to end-stage renal disease has significantly increased and may reach epidemic proportions over the next decade. Regardless of the initial insult, the progression of most forms of renal disease results in tubulo-interstitial fibrosis. This has been closely correlated to the future appearance of renal failure and has therefore been associated with poor long-term prognosis. New molecules and agents to limit the development of tubulo-interstitial fibrosis and slow down the progression towards end-stage renal disease are needed. In the past twenty years, many efforts have been made to understand the mechanisms of tubulo-intersititial fibrosis with the final goal to develop new therapeutic strategies. In this context, this review will focus on the mechanisms and factors involved in the development and the progression of renal fibrosis and will discuss the new promising therapeutic strategies in animal and humans.     

Aerobic exercise can modulate the underlying mechanisms involved in the development of diabetic complications

Diabetes mellitus is a highly prevalent metabolic disorder that affects many molecular pathways, causing a shift from a physiologic to a pathophysiologic state. Alterations in the molecular pathways promote diabetic complications and, thus, many medical and nonmedical therapies have been directed at preventing these complications. Despite the beneficial effects on moderating glycemic control, medical therapies may also have unfavorable side effects. This makes nonmedical therapeutic approaches more attractive due to lower pharmacological side effects of these strategies compared to medical agents. Aerobic exercise is now considered as a major nonmedical strategy that can promote beneficial and protective effects to counteract the development of diabetic complications via attenuation of the major molecular mechanisms involved in diabetes.     

Sclerotial development in Sclerotinia sclerotiorum: awakening molecular analysis of a “Dormant” structure

Sclerotia are hard, asexual, resting structures which can survive for years in soil. In Sclerotinia sclerotiorum, which provides a good model system for studying sclerotial development, sclerotial development has been traditionally divided to three macroscopically distinct stages (initiation, development and maturation). However, additional phases (which can be visualized microscopically) indicate a complex, multi-step, process is involved. Environmental changes, primary metabolism and secondary messengers have been well documented factors affecting sclerotial development, yet analysis of the molecular mechanisms involved in sclerotial development is in its infancy. Here, we review the current status of the known molecular components involved in sclerotial development, with an emphasis on phosphorylative regulation of sclerotial development in S. sclerotiorum. Components such as cAMP-dependent protein kinase, ERK-like mitogen-activated protein kinase and Ser/Thr phosphatases type 2A and 2B, shown to regulate other developmental processes in fungi, have recently been shown to also be involved in regulation of sclerotium development. Reversible protein phosphorylation, as well as additional regulatory mechanisms of gene expression such as DNA methylation and ribosome inactivation, most likely function in concert with secondary metabolites, reactive oxygen species, pH and light in order to regulate sclerotial development in different fungi. The diversity of sclerotium-producing fungi promises to yield exciting variations into the molecular mechanisms regulating this developmental process in different species.     

Use of molecular techniques to elucidate the mechanisms of action of fungal biocontrol agents: a review

Biological control of fungal plant pathogens appears as an attractive and realistic approach, and numerous microorganisms have been identified as biocontrol agents. There have been many efforts to understand the mechanisms of action of fungal biocontrol agents. Microbiological, microscopic, and biochemical techniques applied over many years have shed light on these mechanisms without fully demonstrating them. More recently, the development of molecular techniques has yielded innovative alternative tools for understanding and demonstrating the mechanisms underlying biocontrol properties. To date, more than 70 publications describe the use of molecular techniques for this purpose. They describe work exploiting targeted or non-targeted gene isolation, gene expression profiling, gene inactivation and/or overexpression, the study of regulatory factors. This work has shed considerable light on mechanisms underlying biocontrol properties. It has also fully demonstrated a number of targeted action mechanisms of some biocontrol agents. This review describes the techniques used in such studies, with their potential and limitations. It should provide a guide for researchers wanting to study the molecular basis of the biocontrol in diverse biocontrol agents.     

肌腱再生相关转录因子研究进展

肌腱作为骨骼和肌肉的连接往往容易受到损伤,目前对肌腱基本生物学有限的了解妨碍了肌腱修复技术的发展。最近,一系列肌腱生长相关因子被发现,其中Scleraxis(Scx)和Mohawk(Mkx)已被确定为肌腱生长和分化中的关键转录因子,Sox9和EGR1/2也被报道参与肌腱的生长。然而,目前研究尚未明确这些转录因子的生物学功能及其分子机制。本文就上述转录因子的分布与功能,及转录因子相关分子进行综述,为肌腱的修复提供生物学基础并探讨肌腱损伤治疗的未来发展方向。     

植物WRKY转录因子在应对盐胁迫中的作用研究进展

土壤中的高含盐量严重限制了植物的生长和作物的产量。植物的许多转录因子在植物逆境胁迫中发挥着重要的作用,但仍有很多转录因子的分子机制目前尚不清楚。WRKY转录因子作为高等植物中最大的转录因子家族之一,参与并影响着植物生长发育的多个方面,在盐胁迫的多种不同响应途径中发挥重要作用。WRKY蛋白对基因表达的调控主要是通过与DNA特定顺式调控元件——W-box元件（TTGACC）的结合来实现的。近年来,从模式植物拟南芥（Arabidopsis）到农作物,已经有许多研究揭示了WRKY家族成员的作用和机制。本文综述了WRKY转录因子在应对盐胁迫方面的最新研究进展,探讨了WRKY转录因子研究目前存在的问题和未来的展望。     

Molecular genetic analysis of phototropism in Arabidopsis

Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes.