胚胎发育的精细表观遗传调控

正表观遗传学的概念起源于对进化和发育的研究,早期的表观遗传学涵盖了个体从受精卵到发育成熟过程中的所有事件.而随着对遗传物质的鉴定和DNA双螺旋结构的解析,分子生物学日益成熟起来,科学家们逐渐清楚地意识到,成熟个体的细胞中含有的基因是相同的,但却产生了各种不同的细胞表型.这种基因表达的空间和时间差异性使得科学家们更加明确地进行基因表达调控的研究,从而形成了现代表观遗传学的概念,即不改变DNA序列的可遗传性改变.     

表型可塑性变异的生态-发育机制及其进化意义

表型可塑性赋予生物个体在不同环境条件下通过产生不同表型来维持其适合度的能力.研究结果显示多数可塑性变异的产生是基于对环境变异信号的响应、改变基因表达式样并调整发育轨迹的结果,表观遗传调控体系在基因选择性表达和可塑性变异的跨世代传递过程中发挥了重要作用.不同物种和种群对环境变化的敏感性、发生可塑性变异的能力以及可塑性反应模式不尽相同,预示着控制可塑性能力并独立于控制性状的可塑性基凶的存在,这些基因是直接响应环境信号并控制表型表达的调控基因.表型可塑性不仅是物种适应性进化的一个重要方面,也是选择进化的产物,物种的表型可塑性变异对其生态适应和进化模式有深远的影响.     

异叶苣苔属地上茎的生长式样及其系统发育意义

对异叶苣苔属植物地上茎形态发生过程的观察旨在揭示该属地上茎的生长式样。该研究发现异 叶苣苔属植物地上茎的生长式样并不是以往所认为的简单顶端生长。该属植物的顶芽已完全受到抑制。其地上茎实际上是萌发于小型叶叶腋的侧芽替代顶芽生长所形成的各级侧枝系统,即合轴分枝系统。异叶苣苔属植物地上茎的不分枝情况是位于大型叶叶腋的腋芽受到抑制所致,纯粹是一种次生现象,并不是尖舌苣苔族植物原始祖先的孑遗性状。尖舌苣苔族其他属植物地上茎的生长式样并不均是从异叶苣苔属植物的生长式样演化而来。出蕊苣苔属和异叶苣苔属植物地上茎的生长式样可能来自同一个不太远的祖先,但已经向着不同的方向演化。独叶苣苔属植物复杂的圆锥状对花聚伞花序并非从异叶苣苔属地上茎上部,即生殖生长部分退化而来,乃幼态成熟的复化过程所致。尖舌苣苔属的总状花序可能更接近尖舌苣苔族的原始祖先类型。     

表观遗传调节在神经发育中的生理及病理学意义初探

表观遗传学(epigenetics)研究的是调控遗传物质表达而不改变遗传基因DNA序列所引起的表型变化的过程及其机制。这种变化在细胞生命周期中始终存在,并在数代繁衍过程中保持不变。表观遗传调控过程十分复杂,主要包括DNA甲基化(methylation)、组蛋白修饰(histone modifica-tion)、染色质重塑(chromatin remodeling)、基因印迹(gene imprinting)等,其中DNA甲基化是最为经典的表观遗传调控方式之一,对其了解也最多。本文着重探讨表观遗传调节在神经发育过程中的生理、病理学意义及其分子机制。     

α—SM—肌动蛋白在血管平滑肌细胞重塑过程中的变化及其调控

细胞重塑是细胞在生理、病理情况下发生的形态、结构与功能改变,又称为表型转化。血管平肌细胞具有增殖型和收缩型两种表型,在细胞发育和疾病状态下发生相互转化。α－ＳＭ－肌动蛋白作为血管平滑肌细胞的表型标志,其转化受到因子、细胞外基质等多种因素的调节,对其调节机制的研究发现水及到受体后信号转导途径及其基因调控。     

异三聚体G-蛋白突变对拟南芥生长发育过程的影响

对拟南芥异三聚体G蛋白α-亚基突变体gpa1-3、β-亚基突变体agb1-2及α和β亚基双突变体gpa1agb1与相应的Col野生型的形态特征比较发现,异三聚体G蛋白的突变引起根、叶、生殖器官等的表型发生改变,gpa1-3的叶片宽椭圆形,略大于Col,叶片下表皮细胞显著大于Col、agb1-2及gpa1agb1,果柄也显著长于其它三类,但侧根发生及长角果形态与Col无显著性差异;agb1-2的表型与gpa1agb1的表型相似:叶片小而近圆形、叶缘平滑,侧根发达,长角果较短,这些特征均显著区别于Col及gpa1-3.结果表明,异三聚体G-蛋白在拟南芥的多个生长发育过程中发生作用,且α-亚基和β-亚基在叶、根、花器官等发育过程中的作用不同.     

神经嵴发育调控及颅面部遗传基础研究进展

颅面部赋予脊椎动物无与伦比的进化优势,其由颅神经嵴细胞发育而来的骨、软骨、神经、肌肉等组织组成,使脊椎动物具备了复杂的神经和感官系统。神经嵴细胞是脊椎动物特有的具备迁移性、多能性的细胞类群,它们在增殖、迁移、分化过程中受到多个基因网络的时序调控,从而参与复杂颅面部的形成。同时,颅面部又是一组高度可遗传的表型组合,并具有两个特征：在亲缘后代中的可遗传性及在不同个体间的高度可变性,这两个特征分别提示了颅神经嵴细胞发育调控网络的精准性和可塑性。调控网络内基因适度突变会改变颅神经嵴细胞的增殖和分化从而产生表型可塑性,而有害的遗传突变则将导致畸形产生。本文梳理了对颅面部发育起决定作用的神经嵴细胞的发育过程及基因调控网络,在遗传层面总结了已知的颅面部表型多样性的决定基础和颅面畸形的致病机制,以期为了解颅面部发育过程以及为颅面疾病的防控提供全面认知。     

果蝇发育中细胞决定和分化与基因表达环境

胚胎发育是个程序化的,复杂而有趣的生命现象。在胚胎发育中,不同细胞的分化和其 功能由基因决定,受到核内遗传物质的控制。而细胞的决定和分化则是在不同的细胞质对细胞核的不断作用下,才能逐步进行。核质之间的相互作用先建立特定的基因表达状态,从而选择性表达发育调控基因或分化基因。发育调控基因产物一旦进入胞质,就可改变原来的基因表达环境,使细胞核进入新的基因表达状态,选择表达新的发育调控基因。如果新的发育调控基因的产物再影响细胞核,改变原来的基因表达状态,其它的发育调控基因的表达就可使胚胎细胞进一步分化。在发育过程中,细胞质和细胞核的这个相互作用不断进行,使控制发育程序的不同基因群在特定的时空中表达,受精卵分裂产生的子细胞才能不断决定和逐步分化,最后形成组成个体所必须的各种细胞类型。     

合成生物学在生物基化学品上的应用趋势及展望

合成生物学(synthetic biology)将工程学和生物学相结合, 它不同于对自然基因模拟的基因工程和对代谢途径模拟的代谢工程,而是在以基因组解析技术和化学合成技术为核心的现代生物技术基础上,以系统生物学思想和知识为指导,综合生物化学、生物物理和生物信息技术,建立基于基因和基因组、蛋白质和蛋白质组的基本要素(模块)及其组合的工程化的资源库和技术平台,旨在设计、改造、重建或制造生物分子、生物部件、生物系统、代谢途径与发育分化过程,以及具有生命活动能力的细胞和生物个体.     

对ERP非专业成员有用的遗传术语词汇表（6）

嵌合体 由两种或多种不同表型组织构成的个体。可通过普通杂交或混合不同类型的早期胚胎细胞获得。 条件转基因技术 将基因修饰限定于特定的组织或细胞,或在胚胎、动物发育的不同时间点,或使其被特定的信号（如某一化学物质的注射）激活。 基因构建（或转基因） 一段包含目的DNA序列的人工获得的DNA片段。     

The pre-Mendelian, pre-Darwinian world: Shifting relations between genetic and epigenetic mechanisms in early multicellular evolution

The reliable dependence of many features of contemporary organisms on changes in gene content and activity is tied to the processes of Mendelian inheritance and Darwinian evolution. With regard to morphological characters, however, Mendelian inheritance is the exception rather than the rule, and neo-Darwinian mechanisms in any case do not account for the origination (as opposed to the inherited variation) of such characters. It is proposed, therefore, that multicellular organisms passed through a pre-Mendelian, pre-Darwinian phase, whereby cells, genes and gene products constituted complex systems with context-dependent, self-organizing morphogenetic capabilities. An example is provided of a plausible ’core’ mechanism for the development of the vertebrate limb that is both inherently pattern forming and morphogenetically plastic. It is suggested that most complex multicellular structures originated from such systems. The notion that genes are privileged determinants of biological characters can only be sustained by neglecting questions of evolutionary origination and the evolution of developmental mechanisms.     

A topological look into the evolution of developmental programs

Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describing the intertwined network of spatiotemporal processes underlying the development of complex multicellular organisms. Nonetheless, an overview of developmental trajectories can be obtained from cell type lineage maps. Here, we propose that these lineage maps can also reveal how developmental programs evolve: the modes of evolving new cell types in an organism should be visible in its developmental trajectories and therefore in the geometry of its cell type lineage map. This idea is demonstrated using a parsimonious generative model of developmental programs, which allows us to reliably survey the universe of all possible programs and examine their topological features. We find that, contrary to belief, tree-like lineage maps are rare, and lineage maps of complex multicellular organisms are likely to be directed acyclic graphs in which multiple developmental routes can converge on the same cell type. Although cell type evolution prescribes what developmental programs come into existence, natural selection prunes those programs that produce low-functioning organisms. Our model indicates that additionally, lineage map topologies are correlated with such a functional property: the ability of organisms to regenerate.     

Morphogenesis by coupled regulatory networks: Reliable control of positional information and proportion regulation

Based on a non-equilibrium mechanism for spatial pattern formation we study how position information can be controlled by locally coupled discrete dynamical networks, similar to gene regulation networks of cells in a developing multicellular organism. As an example we study the developmental problems of domain formation and proportion regulation in the presence of noise, as well as in the presence of cell flow. We find that networks that solve this task exhibit a hierarchical structure of information processing and are of similar complexity as developmental circuits of living cells. Proportion regulation is scalable with system size and leads to sharp, precisely localized boundaries of gene expression domains, even for large numbers of cells. A detailed analysis of noise-induced dynamics, using a mean-field approximation, shows that noise in gene expression states stabilizes (rather than disrupts) the spatial pattern in the presence of cell movements, both for stationary as well as growing systems. Finally, we discuss how this mechanism could be realized in the highly dynamic environment of growing tissues in multicellular organisms.     

Genetic programming of development: A model

Abstract. Genetic programming of the developmental processes in multicellular organisms is proposed to be so intricate and vitally important that a large set of genes is dedicated solely to this end. It is further proposed that this set can be compartmentalized into subsets on the basis of the changes in gene activities that occur during ontogenesis, and that the genes in each subset transiently control the epigenetic activities of a small group of cells. Automatic subset activation is achieved by the product of a gene in each subset that transfers activity specifically to the subset next in the developmental sequence. This device can generate a unidirectional series of activations that cascade hierarchically through development like toppling dominoes. The model provides a basis for developmental phenomena, such as pattern formation, morphogenesis, and regeneration, and it makes testable predictions at the molecular level.     

Spatiotemporal reorganization of growth rates in the evolution of ontogeny

Abstract. Heterochrony, evolutionary changes in rate or timing of development producing parallelism between ontogeny and phylogeny, is viewed as the most common type of evolutionary change in development. Alternative hypotheses such as heterotopy, evolutionary change in the spatial patterning of development, are rarely entertained. We examine the evidence for heterochrony and heterotopy in the evolution of body shape in two clades of piranhas. One of these is the sole case of heterochrony previously reported in the group; the others were previously interpreted as cases of heterotopy. To compare ontogenies of shape, we computed ontogenetic trajectories of shape by multivariate regression of geometric shape variables (i.e., partial warp scores and shape coordinates) on centroid size. Rates of development relative to developmental age and angles between the trajectories were compared statistically. We found a significant difference in developmental rate between species of Serrasalmus , suggesting that heterochrony is a partial explanation for the evolution of body shape, but we also found a significant difference between their ontogenetic transformations; the direction of the difference between them suggests that heterotopy also plays a role in this group. In Pygocentrus we found no difference in developmental rate among species, but we did find a difference in the ontogenies, suggesting that heterotopy, but not heterochrony, is the developmental basis for shape diversification in this group. The prevalence of heterotopy as a source of evolutionary novelty remains largely unexplored and will not become clear until the search for developmental explanations looks beyond heterochrony.     

Cellular oscillators in animal segmentation

Kinetic modeling of developmental dynamics requires detailed knowledge about genetic and metabolic networks that underlie developmental processes. However, such knowledge is not available for a vast majority of developmental processes. Here, we present an coarse-grained, phenomenological model of periodic pattern formation in multicellular organisms based on cellular oscillators (CO) that can be applied to systems for which little or no molecular data is available. An oscillatory process within cells serves as a developmental clock whose period is tightly regulated by cell-autonomous and non-autonomous mechanisms. A spatial pattern is generated as a result of an initial temporal ordering of the cell oscillators freezing into spatial order as the clocks slow down and stop at different times or phases in their cycles. When applied to vertebrate somitogenesis, the CO model can reproduce the dynamics of periodic gene expression patterns observed in the presomitic mesoderm. Different somite lengths can be generated by altering the period of the oscillation. There is evidence that a CO-type mechanism might also underlie segment formation in certain invertebrates, such as annelids and short germ insects. This suggests that the dynamical principles of sequential segmentation might be equivalent throughout the animal kingdom although most of the genes involved in segment determination differ between distant phyla.     

Phenotypic and dynamical transitions in model genetic networks. I. Emergence of patterns and genotype-phenotype relationships

SUMMARY Genotype–phenotype interactions during the evolution of form in multicellular organisms is a complex problem but one that can be aided by computational approaches. We present here a framework within which developmental patterns and their underlying genetic networks can be simulated. Gene networks were chosen to reflect realistic regulatory circuits, including positive and negative feedback control, and the exchange of a subset of gene products between cells, or within a syncytium. Some of these networks generate stable spatial patterns of a subset of their molecular constituents, and can be assigned to categories (e.g., "emergent" or "hierarchic") based on the topology of molecular circuitry. These categories roughly correspond to what has been discussed in the literature as "self-organizing" and "programmed" processes of development. The capability of such networks to form patterns of repeating stripes was studied in network ensembles in which parameters of gene-gene interaction were caused to vary in a manner analogous to genetic mutation. The evolution under mutational change of individual representative networks of each category was also simulated. We have found that patterns with few stripes (≤3) are most likely to originate in the form of a hierarchic network, whereas those with greater numbers of stripes (≥4) originate most readily as emergent networks. However, regardless of how many stripes it contains, once a pattern is established, there appears to be an evolutionary tendency for emergent mechanisms to be replaced by hierarchic mechanisms. These results have potential significance for the understanding of genotype-phenotype relationships in the evolution of metazoan form.     

Genetic programming of development: A model

Genetic programming of the developmental processes in multicellular organisms is proposed to be so intricate and vitally important that a large set of genes is dedicated solely to this end. It is further proposed that this set can be compartmentalized into subsets on the basis of the changes in gene activities that occur during ontogenesis, and that the genes in each subset transiently control the epigenetic activities of a small group of cells. Automatic subset activation is achieved by the product of a gene in each subset that transfers activity specifically to the subset next in the developmental sequence. This device can generate a unidirectional series of activations that cascade hierarchically through development like toppling dominoes. The model provides a basis for developmental phenomena, such as pattern formation, morphogenesis, and regeneration, and it makes testable predictions at the molecular level.     

Environmentally induced responses co-opted for reproductive altruism

Reproductive altruism is an extreme form of altruism best typified by sterile castes in social insects and somatic cells in multicellular organisms. Although reproductive altruism is central to the evolution of multicellularity and eusociality, the mechanistic basis for the evolution of this behaviour is yet to be deciphered. Here, we report that the gene responsible for the permanent suppression of reproduction in the somatic cells of the multicellular green alga, Volvox carteri, evolved from a gene that in its unicellular relative, Chlamydomonas reinhardtii, is part of the general acclimation response to various environmental stress factors, which includes the temporary suppression of reproduction. Furthermore, we propose a model for the evolution of soma, in which by simulating the acclimation signal (i.e. a change in cellular redox status) in a developmental rather than environmental context, responses beneficial to a unicellular individual can be co-opted into an altruistic behaviour at the group level. The co-option of environmentally induced responses for reproductive altruism can contribute to the stability of this behaviour, as the loss of such responses would be costly for the individual. This hypothesis also predicts that temporally varying environments, which will select for more efficient acclimation responses, are likely to be more conducive to the evolution of reproductive altruism.