A molecular gradient in early Drosophila embryos and its role in specifying the body pattern

After fertilization, the protein products of the Drosophila homeobox gene caudal (cad) accumulate in a concentration gradient spanning the anteroposterior axis of the developing embryo. Mutations in the cad gene that reduce or eliminate the gradient cause abnormal zygotic expression of at least one segmentation gene (fushi tarazu) and alter the global body pattern.     

The molecular mechanism of embryonic stem cell pluripotency maintenance

In vitro cultured embryonic stem （ES） cells are derived from the inner cell mass （ICM） of pre-implantation embryos, and are capable of giving rise to all cell and tissue types of the three germ layers upon being injected back into blastocysts. These ceils are therefore said to possess pluripotency that can be maintained infinitely in culture under optimal conditions. Such pluripotency maintenance is believed to be due to the symmetrical cleavage of the cells in an undifferentiated state. The pluripotency of ES cells is the basis for their various practical and potential applications. ES cells can be used as donor cells to generate knockout or transgenic animals, as in vitro models of mammalian development, and as cell resources for cell therapy in regenerative medicine. The further success in these applications, particularly in the last two, is dependent on the establishment of a culture system with components in the medium clearly defined and the subsequent procedures for controlled differentiation of the cells into specific lineages. In turn, elucidating the molecular mechanism for pluripotency maintenance of ES cells is the prerequisite. This paper summarizes the recent progresses in this area, focusing mainly on the LIF/STAT3, BMPs/Smads, canonical Wnt, TGFβ/activin/nodal, PI3K and FGF signaling pathways and the genes such as oct4, nanog that are crucial in ES cell pluripotency maintenance. The regulatory systems of pluripotency maintenance in both mouse and human ES cells are also discussed. We believe that the cross-talkings between these signaling pathways, as well as the regulatory system underlying pluripotency maintenance will be the main focus in the area of ES cell researches in the future.     

Drosophila and the genetics of the internal milieu

'Homeostasis', from the Greek words for 'same' and 'steady', refers to ways in which the body acts to maintain a stable internal environment despite perturbations. Recent studies in Drosophila exemplify the conservation of regulatory mechanisms involved in metabolic homeostasis. These new findings underscore the use of Drosophila as a model for the study of various human disorders.     

果蝇分子群体遗传研究分析方法概述

果蝇属物种长期以来被作为基础生物学、特别是群体和进化遗传学的模式物种,来探讨生物学中的一些基本问题,如物种形成的遗传机制、新基因的起源及其方式、适应性进化的遗传机制等.群体遗传的方法贯穿于遗传学、生态学、古生物学、系统发育学等领域之中,已渐成为基础生物学研究的重要方法.围绕果蝇群体遗传研究中的3个主要问题,即起源地、群体历史动态和群体遗传结构,就当前用于分析上述问题的方法进行了概述,并强调了发展适用于多个座位数据的分析方法是将来的一个重要发展方向.     

Robustness of the BMP morphogen gradient in Drosophila embryonic patterning

Developmental patterning relies on morphogen gradients, which generally involve feedback loops to buffer against perturbations caused by fluctuations in gene dosage and expression. Although many gene components involved in such feedback loops have been identified, how they work together to generate a robust pattern remains unclear. Here we study the network of extracellular proteins that patterns the dorsal region of the Drosophila embryo by establishing a graded activation of the bone morphogenic protein (BMP) pathway. We find that the BMP activation gradient itself is robust to changes in gene dosage. Computational search for networks that support robustness shows that transport of the BMP class ligands (Scw and Dpp) into the dorsal midline by the BMP inhibitor Sog is the key event in this patterning process. The mechanism underlying robustness relies on the ability to store an excess of signalling molecules in a restricted spatial domain where Sog is largely absent. It requires extensive diffusion of the BMP-Sog complexes, coupled with restricted diffusion of the free ligands. We show experimentally that Dpp is widely diffusible in the presence of Sog but tightly localized in its absence, thus validating a central prediction of our theoretical study.     

甲烷分子结构的对称性在形成分子轨道中的应用

本文通过两种途径形成甲烷的分子轨道,研究了对称性在分子轨道及杂化轨道的形成中起的重要作用,并得出两种方法形成甲烷分子轨道是一样的．     

Characteristic folding pattern of polytene chromosomes in Drosophila salivary gland nuclei

A computer-based system for recording and analysing light microscope images, combined with classical cytogenetic analysis, has revealed the spatial organization of the giant chromosomes of Drosophila salivary gland cells. Each polytene chromosome arm folds up in a characteristic way, contacts the nuclear surface at specific sites and is topologically isolated from all other arms.     

Preferential binding of imaginal disk cells to embryonic segments of Drosophila

Cell recognition and selective adhesion may be important in pattern formation; such processes in Drosophila melanogaster could be responsible for the maintenance of segment boundaries, the morphogenesis of metamorphosing imaginal disks, and the paths of axon outgrowth during neurogenesis. As cells from different imaginal disks of Drosophila are able to recognize and sort out from one another, we decided to investigate whether these larval cells could recognize and bind to the epidermis of intact embryos. We report here that imaginal disk cells bind preferentially to the epidermis of the embryonic segments from which they are derived: thoracic disk cells to thoracic segments and genital disk cells to abdominal segments. Furthermore, thoracic disk cells recognize and bind, without preference, to all segments of the homoeotic mutant Df(3R)P9 (ref. 6). We conclude, therefore, that cells of the same segmental origin have similar recognition properties at different developmental stages.     

Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics

Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions--a temperature step--in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100 min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development.     

Surface mechanics mediate pattern formation in the developing retina

Pattern formation of biological structures involves organizing different types of cells into a spatial configuration. In this study, we investigate the physical basis of biological patterning of the Drosophila retina in vivo. We demonstrate that E- and N-cadherins mediate apical adhesion between retina epithelial cells. Differential expression of N-cadherin within a sub-group of retinal cells (cone cells) causes them to form an overall shape that minimizes their surface contact with surrounding cells. The cells within this group, in both normal and experimentally manipulated conditions, pack together in the same way as soap bubbles do. The shaping of the cone cell group and packing of its components precisely imitate the physical tendency for surfaces to be minimized. Thus, simple patterned expression of N-cadherin results in a complex spatial pattern of cells owing to cellular surface mechanics.     

Electrically induced structure formation and pattern transfer

The wavelength of light represents a fundamental technological barrier to the production of increasingly smaller features on integrated circuits. New technologies that allow the replication of patterns on scales less than 100 nm need to be developed if increases in computing power are to continue at the present rate. Here we report a simple electrostatic technique that creates and replicates lateral structures in polymer films on a submicrometre length scale. Our method is based on the fact that dielectric media experience a force in an electric field gradient. Strong field gradients can produce forces that overcome the surface tension in thin liquid films, inducing an instability that features a characteristic hexagonal order. In our experiments, pattern formation takes place in polymer films at elevated temperatures, and is fixed by cooling the sample to room temperature. The application of a laterally varying electric field causes the instability to be focused in the direction of the highest electric field. This results in the replication of a topographically structured electrode. We report patterns with lateral dimensions of 140 nm, but the extension of the technique to pattern replication on scales smaller than 100 nm seems feasible.     

In vivo binding pattern of a trans-regulator of homoeotic genes in Drosophila melanogaster

The specification and maintenance of the metameric pattern in Drosophila melanogaster is regulated by complicated gene interactions. The differential expression of the homoeotic genes of the Antennapedia complex (ANT-C) and bithorax complex (BX-C), which determine segmental identities, is partly controlled by cross-regulatory interactions of loci within the two clusters and partly by trans-acting factors located outside the two complexes. One of the trans-regulatory genes, Polycomb (Pc), acts as a repressor of the ANT-C and BX-C. Mutations of Polycomb result in a complete depression of the homoeotic genes, leading to abdominal transformations of all body segments. Polycomb is part of a large class of trans-regulatory genes (Pc-group), estimated to comprise up to 40 loci. We have raised antibodies against the Polycomb protein, and, using an improved immunostaining technique, showed that the Polycomb protein binds to 60 discrete sites along the polytene chromosomes of salivary glands. These sites comprise the ANT-C and the BX-C as well as several locations of Pc-group genes. This is the first clear evidence for a direct interaction of Polycomb with homoeotic loci and other Pc-group genes.     

An embryonic pattern of expression of a human fetal globin gene in transgenic mice

During the evolution of the beta-globin family gene in vertebrates, different globin genes acquired different developmental patterns of expression. In mammals, specific 'embryonic' beta-like globins are synthesized in the earliest erythroid cells, which differentiate in the yolk sac of the embryo. In most mammals the embryonic globin chains are replaced by 'adult' beta-globins in fetal and adult erythrocytes, which arise in the liver and bone marrow, respectively. However, in simian primates (including humans), a distinct 'fetal' type of beta-like globin chain predominates in fetal erythroid cells. Based on the pattern of DNA sequence homologies between different mammalian species, these fetal globin genes, G gamma and A gamma, are thought to have descended from an ancestral gene, 'proto-gamma', which was embryonic in its pattern of expression. In the mouse, as well as in most other mammalian species, the descendants of the proto-gamma gene continue to function as embryonic genes. To investigate the evolutionary changes that led to the 'fetal recruitment' of the gamma-globin genes in primates, we have introduced the cloned human G gamma-globin gene into the mouse germ line. We report here that the human G gamma gene reverts to an embryonic pattern of expression in the developing mouse. This observation suggests that during evolution a shift occurred in the timing of expression of a trans-acting signal controlling the proto-gamma gene.