Experimental embryologic, biochemical and molecular biology approaches to the identification of embryonic inducers

Problems of the mechanisms of embryonic induction in vertebrate development have been considered on the basis of author's experimental data. Though several polypeptide factors with certain inducing activity have been identified recently, molecular genetic mechanisms of their effect on embryonic target cells remains largely unclear. One of possible causes of very slow progress in this area of developmental biology is an inadequate system of biotesting of inducers at tissue level (ectoderm of early amphibian gastrulae) using histological criteria. A necessity for carrying out similar studies on cellular level and estimating effect of inducers using immunochemical and molecular biological methods has been postulated. Methods allowing to carry out biotesting of inducers on cell suspension or aggregate of a one type of embryonic cells have been proposed. New approaches, combining the methods of experimental embryology and molecular biology, to studies of embryonic inducers, receptors, and their mRNA, have been analyzed.     

Michael Akam and the rise of evolutionary developmental biology

Michael Akam has been awarded the 2007 Kowalevsky medal for his many research accomplishments in the area of evolutionary developmental biology. We highlight three tributaries of Michael’s contribution to evolutionary developmental biology. First, he has made major contributions to our understanding of development of the fruit fly, Drosophila melanogaster. Second, he has maintained a consistent focus on several key problems in evolutionary developmental biology, including the evolving role of Hox genes in arthropods and, more recently, the evolution of segmentation mechanisms. Third, Michael has written a series of influential reviews that have integrated progress in developmental biology into an evolutionary perspective. Michael has also made a large impact on the field through his effective mentorship style, his selfless promotion of younger colleagues, and his leadership of the University Museum of Zoology at Cambridge and the European community of evolutionary developmental biologist.     

Muscle building; mechanisms of myotube guidance and attachment site selection

The complex muscle patterns of higher organisms arise as migrating myoblasts are guided toward and connect with specific attachment sites. We review here the current understanding of myotube migration, focusing on its dynamic nature and the few molecular cues that have been identified to date. Much of this knowledge comes from studies in Drosophila, where powerful methods for in vivo imaging and genetic manipulation can be used to tackle this important but largely unsolved problem in developmental biology.     

Fungal evolution and speciation

Molecular-genetic methods are making possible a revolution in the the study of fungal evolutionary biology. To date, substantial progress has been made toward the goal of determining phylogenetic relationships, This is particularly true for higher taxonomic levels, where small-subunit rRNA sequences have proved valuable. The tremendous range of life-cycle diversity exhibited among fungi makes them excellent candidates for exploring areas of evolutionary biology that are as yet poorly investigated, particularly in terms of population biology, reproductive strategies and speciation. This argument is supported by the results of recent studies.     

Four decades of teaching developmental biology in Germany

I have taught developmental biology in Essen for 30 years. Since my department is named Zoophysiologie (Zoophysiology), besides Developmental Biology, I also have to teach General Animal Physiology. This explains why the time for teaching developmental biology is restricted to a lecture course, a laboratory course and several seminar courses. However, I also try to demonstrate in the lecture courses on General Physiology the close relationship between developmental biology, physiology, morphology, anatomy, teratology, carcinogenesis, evolution and ecology (importance of environmental factors on embryogenesis). Students are informed that developmental biology is a core discipline of biology. In the last decade, knowledge about molecular mechanisms in different organisms has exponentially increased. The students are trained to understand the close relationship between conserved gene structure, gene function and signaling pathways, in addition to or as an extension of, classical concepts. Public reports about the human genome project and stem cell research (especially therapeutic and reproductive cloning) have shown that developmental biology, both in traditional view and at the molecular level, is essential for the understanding of these complex topics and for serious and non-emotional debate.     

Development of the cardiac pacemaking and conduction system

The heartbeat is initiated and coordinated by a heterogeneous set of tissues, collectively referred to as the pacemaking and conduction system (PCS). While the structural and physiological properties of these specialized tissues has been studied for more than a century, distinct new insights have emerged in recent years. The tools of molecular biology and the lessons of modern embryology are beginning to uncover the mechanisms governing induction, patterning and developmental integration of the PCS. In particular, significant advances have been made in understanding the developmental biology of the fast conduction network in the ventricles--the His-Purkinje system. Although this progress has largely been made by using animal models such as the chick and mouse, the insights gained may help explain cardiac disease in humans, as well as lead to new treatment strategies.     

植物雄性不育基因工程的研究及应用(综述)

本文基于植物花粉花药的发育分子生物学研究成果,介绍了几种创造基因工程核雄性不育系和胞质雄性不育系的途径,保持与恢复基因工程雄性不育系的途径和雄性不育基因工程应用中亟待解决的问题.     

Integrating ecology and developmental biology to explain the timing of frog metamorphosis

Amphibian metamorphosis has long intrigued ecologists and developmental biologists, yet the two research programs have progressed separately and toward different goals. Plasticity in metamorphic timing has profound effects on fitness, which has prompted ecologists to develop and test models for predicting how environmental factors affect the size and age of metamorphosis. These models rely upon untested assumptions about the mechanisms for regulating growth and development. Whereas developmental biologists explicitly investigate these mechanisms at the hormonal and genetic levels, they largely ignore the role of environmental input. Recent developments in our understanding of the molecular biology of frog metamorphosis are revealing how these two research programs could be integrated. Here, I review these developments to test ecologists' assumptions about frog metamorphosis, and to present strategies for both research fields to investigate the mechanistic basis of metamorphic plasticity.     

Reproductive/urogenital organ development and molecular genetic cascades: glamorous developmental processes of bodies

At the beginning of the 21st century, developmental biologists together with medical researchers in a wide range of fields are witnessing rapid progress in molecular developmental biology. For example, conditional gene knockout systems are being designed to tackle questions about organogenesis and body plan formation in experimental mouse models and experimental designs include several compound mutant analyses and genome modification strategies. On the other hand, several fields remain relatively unexplored. Molecular mechanisms of sex differentiation are one of the unexplored huge area. Unanswered questions include the molecular genetic cascade of gonad formation, reproductive organ formation, uterus, external genitalia and mammary gland formation, and also the molecular mechanisms of signal transduction, and gene regulation by nuclear hormone receptors. This special thematic review series entitled, "Reproductive/urogenital organ development and molecular genetic cascades: glamorous developmental processes of bodies," covers such a wide range of topics. For this special issue, I have asked active researchers to contribute reviews of these topics which I believe will be useful not only for molecular developmental biologists, but also for researchers in biochemistry and cell biology. It will be my great pleasure if this special thematic issue encourages scientists to study this exciting research field.     

心脏发育过程中的信号调控机制研究

我国是出生缺陷高发国家,其中先天性心脏病在各类出生缺陷中居于首位,严重地影响我国的人口素质.同样,后天性心脏血管疾病（心血管疾病）也是影响国民健康和社会发展的主要疾病.近年来研究表明,所谓＂后天性＂心脏血管疾病虽然大多不在胚胎期表现出功能异常,但遗传因素在发病过程中也起关键作用,因此,＂后天性＂心血管疾病也有其发育生物学基础.在一些心血管疾病中,胚胎发育基因如ANF和β-MHC的表达说明胚胎发育的某些机制参与了发病过程.由于出生缺陷和心血管疾病的防治是我国公共卫生和社会发展中亟待解决的重大健康问题,了解心血管系统正常发生发育规律和机制及发病机理并在此基础上建立新的防治策略和防治措施是生命科学需要解决的重大基础科学问题.本文主要综述了目前模式动物,特别是小鼠心脏发育过程中的信号传导调控机制的研究现状及进展.     

Small molecules and chemical tools at the interface

As our understanding of the molecular mechanisms driving complex biological processes grows, the role of chemical biology will continue to expand. The 2008 American Society for Biochemistry and Molecular Biology meeting showcased recent progress in the field of chemical biology while simultaneously pointing toward the future of research at the interface between chemistry and biology.     

The evolution of molecular biology into systems biology

Systems analysis has historically been performed in many areas of biology, including ecology, developmental biology and immunology. More recently, the genomics revolution has catapulted molecular biology into the realm of systems biology. In unicellular organisms and well-defined cell lines of higher organisms, systems approaches are making definitive strides toward scientific understanding and biotechnological applications. We argue here that two distinct lines of inquiry in molecular biology have converged to form contemporary systems biology.     

Generation of transgenic birds with replication-deficient lentiviruses

Birds are of great interest as an animal model in biological research and for commercial applications as a bioreactor. Effective methods for manipulating the avian genome would accelerate progress in fields such as developmental biology and behavioral neurobiology, which traditionally have relied on birds as model systems for biological research. Here we describe a simple and effective protocol for producing transgenic birds using lentiviral vectors that can be used to achieve tissue-specific transgene expression at high levels. The time allotted for the procedure depends upon the species of bird; adult transgenic quails can be generated in approximately 5 months.     

多能干细胞体外分化为类神经管模型的研究进展

近年来多能干细胞(PSCs)的体外培养与分化技术发展迅速,并广泛应用于再生医学和发育生物学等领域。PSCs能够在体外神经诱导的条件下分化为类神经管模型,这为探索体内早期神经发育与中枢神经系统发育疾病的形成机制提供了全新的实验平台。本文总结了近年来应用小鼠和人PSCs建立体外类神经管模型的研究进展,其中体外模型主要包括在不同培养体系下诱导获得的二维(2D)与三维(3D)类神经管模型,并针对早期类神经管模型在神经系统发育性疾病机制研究中的前景和挑战作进一步探讨,同时为疾病预防和治疗提供新的思路。     

Development and mechanistic explanation

Within modern philosophy of biology the topic of mechanistic explanation has become a central theme for critical discussion. The neo-mechanical philosophers have developed accounts that emphasize intervention and manipulation as the central epistemic tools that allow gaining epistemic access upon the mechanisms and have argued that the processes of inter-field integration across disciplines can be understood through the analysis of mechanisms spanning multiple levels. In this paper I revisit current proposals on mechanistic explanation in order to show some of their limitations when dealing with developmental mechanisms. I basically argue that (i) developmental mechanisms cannot be accommodated within a framework centered upon the mutual manipulation principle, (ii) the distinction between causal relations vs. constitutive relations cannot be easily demarcated within developmental biology and (iii) the notion of "part" underlying the neo-mechanical accounts on explanation is not suitable for developmental biology.     

The interface between cell and developmental biology

Cell differentiation, morphology, migration, polarity, intercellular communication and adhesion are all cellular processes that control embryo morphogenesis and lie at the interface of cell and developmental biology. The interface between these two fields is best illustrated, however, in studies of axiation and cytoskeletal remodeling during development. Recent advances reveal novel mechanisms for axiation, including the role of RNA and protein degradation in regulating the timely expression of morphogenetic signals. Significant progress has also been made in identifying components of the cytoskeleton and the extracellular matrix that mediate embryonic cell migration and polarity. Cellular processes at the interface of cell and developmental biology are overseen by the Wnt signaling cascade that coordinates both axiation and cytoskeletal remodeling during development.     

Drosophila follicle cells: morphogenesis in an eggshell

Epithelial morphogenesis is important for organogenesis and pivotal for carcinogenesis, but mechanisms that control it are poorly understood. The Drosophila follicular epithelium is a genetically tractable model to understand these mechanisms in vivo. This epithelium of follicle cells encases germline cells to create an egg. In this review, we summarize progress toward understanding mechanisms that maintain the epithelium or permit migrations essential for oogenesis. Cell-cell communication is important, but the same signals are used repeatedly to control distinct events. Understanding intrinsic mechanisms that alter responses to developmental signals will be important to understand regulation of cell shape and organization.     

Morphogenetic fields in embryogenesis, regeneration, and cancer: Non-local control of complex patterning

Establishment of shape during embryonic development, and the maintenance of shape against injury or tumorigenesis, requires constant coordination of cell behaviors toward the patterning needs of the host organism. Molecular cell biology and genetics have made great strides in understanding the mechanisms that regulate cell function. However, generalized rational control of shape is still largely beyond our current capabilities. Significant instructive signals function at long range to provide positional information and other cues to regulate organism-wide systems properties like anatomical polarity and size control. Is complex morphogenesis best understood as the emergent property of local cell interactions, or as the outcome of a computational process that is guided by a physically encoded map or template of the final goal state? Here I review recent data and molecular mechanisms relevant to morphogenetic fields: large-scale systems of physical properties that have been proposed to store patterning information during embryogenesis, regenerative repair, and cancer suppression that ultimately controls anatomy. Placing special emphasis on the role of endogenous bioelectric signals as an important component of the morphogenetic field, I speculate on novel approaches for the computational modeling and control of these fields with applications to synthetic biology, regenerative medicine, and evolutionary developmental biology.