A morphomechanical aspect of epigenesis

Epigenesis in classical embryology is regarded as self-complication of spatial organization of the embryo during its development. The reality of the phenomenon of self-complication at the cellular and supra-cellular levels has been demonstrated by classical experimental embryology. Today, in light of studies of cell differentiation mechanisms, this problem acquired a molecular aspect. However, the attempt to solve it within the limits of molecular level leads to the paradox of “irreducible complexity.” The discovery of a physical factor that concurrently would influence the processes of supracellular and molecular levels would be the best way to solve the problem of self-complication. The mechanical tension in cells and tissues of a developing organism may play the role of such factor. The paper considers facts on the role of mechanical stresses in morphogenesis and gene expression.     

Craniofacial development and the evolution of the vertebrates: the old problems on a new background

Based on recent advances in experimental embryology and molecular genetics, the morphogenetic program for the vertebrate cranium is summarized and several unanswered classical problems are reviewed. In particular, the presence of mesodermal segmentation in the head, the homology of the trabecular cartilage, and the origin of the dermal skull roof are discussed. The discovery of the neural-crest-derived ectomesenchyme and the roles of the homeobox genes have allowed the classical concept of head segmentation unchanged since Goethe to be re-interpreted in terms of developmental mechanisms at the molecular and cellular levels. In the context of evolutionary developmental biology, the importance of generative constraints is stressed as the developmental factor that generates the homologous morphological patterns apparent in various groups of vertebrates. Furthermore, a modern version of the germ-layer theory is defined in terms of the conserved differentiation of cell lineages, which is again questioned from the vantage of evolutionary developmental biology.     

Contribution of the Belgian school of embryology to the concept of neural induction by the organizer

Albert BRACHET, founder of the Brussels School of embryology, conducted delicate experiments in which he selectively destroyed zones of the grey crescent with heated needles. This allowed him to observe, in 1923, that the median region of the grey crescent of the blastula is a area of spontaneous differentiation and that this "primary self-differentiation centre" organizes the axial organs in anurans. It is thus fair to say that A. BRACHET contributed significantly to the emergence of the organizer concept. Albert DALCQ and Jean PASTEELS, successors of A. BRACHET, trying to solve the problem of the organizer's determination, proposed their famous quantitative theory of embryonic development resulting in the concept of morphogenetic potential, which increases with the CV concentration, a combination of a cortical constituent C and a vegetal substance V. Jean BRACHET, the younger son of A. BRACHET and one of the founding father of molecular biology and embryology, was soon convinced that the organizer owes its inducing power to a chemical substance. Being the first to suggest the role of RNA in protein synthesis, he first imagined that RNA could be the active substance in induction but became convinced afterwards that the inducer must have a proteic nature. His interest in the molecular aspects of induction stimulated research that was to make chemical embryology molecular.     

Modern evolutional developmental biology: Mechanical and molecular genetic or phenotypic approaches?

Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.     

Theoretical considerations on cell ensembles

Structure-function interdependency must apply at the supracellular level as well as at cellular and molecular levels. The overall structure and the intercellular geometry of the multicellular erythroblastic island, although strongly dependent upon molecular interactions (which determine or modulate recognition, adhesion, and the like), also carry consequences at a more general physical-chemical level. These relate to such factors as local concentrations and gradients, the nature of the forces and the phase-state of the material in the intercellular region, the generalized intercellular transport processes (diffusional, osmotic, electrokinetic, hydrodynamic, etc.), and the dynamic coupling of flows. Such "other-level" phenomena must play a significant role, and therefore must be taken into account, in formulating a comprehensive picture of the ways in which the microenvironment acts in the management and control of the processes of hematopoietic differentiation and development.     

Application of microinjection techniques to plant nutrition

To gain a full understanding of the complex processes that underlie plant nutrition requires the elucidation of the genetic, molecular, biochemical, biophysical, physiological and environmental factors that interact, at the cellular, organ and whole plant levels, to allow this sessile organism to optimize the allocation and utilization of available resources. The application of microinjection methods, in conjunction with molecular tools, established a powerful experimental approach to elucidate the processes underlying plant growth and development. Besides providing insight into the molecular nature of many of the membrane transport systems that function in nutrient acquisition and transport, this approach revealed the presence of a unique plasmodesmal macromolecular trafficking system that operates at the cellular/tissue and whole-plant level. This information processing network it discussed in terms of its role in allowing plants to regulate physiological activities at a supracellular level. Future studies aimed at identifying additional genes associated with this plasmodesmal macromolecular trafficking system will advance our understanding of the function and evolution of this novel plant communication system.     

Mechanotransduction pathways in skeletal muscle hypertrophy

In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process.     

Mechanotransduction pathways in skeletal muscle hypertrophy

In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process.     

Structural and regulatory functions of keratins

The diversity of epithelial functions is reflected by the expression of distinct keratin pairs that are responsible to protect epithelial cells against mechanical stress and to act as signaling platforms. The keratin cytoskeleton integrates these functions by forming a supracellular scaffold that connects at desmosomal cell-cell adhesions. Multiple human diseases and murine knockouts in which the integrity of this system is destroyed testify to its importance as a mechanical stabilizer in certain epithelia. Yet, surprisingly little is known about the precise mechanisms responsible for assembly and disease pathology. In addition to these structural aspects of keratin function, experimental evidence accumulating in recent years has led to a much more complex view of the keratin cytoskeleton. Distinct keratins emerge as highly dynamic scaffolds in different settings and contribute to cell size determination, translation control, proliferation, cell type-specific organelle transport, malignant transformation and various stress responses. All of these properties are controlled by highly complex patterns of phosphorylation and molecular associations.     

Apoptose au cours de la spermatogenèse et dans le sperme éjaculé

It has become clear in recent years that programmed cell death occurs spontaneously in the cycle of the seminiferous epithelium. Induced germ cell apoptosis occurs at specific stages of the spermatogenic cycle and the existence of supracellular control of germ cell death during spermatogenesis has been documented. If apoptosis is a key phenomenon in the control of sperm production, the existence and role of apoptosis in ejaculated sperm cells remain controversial. Apoptosis — as determined by DNA fragmentation (TUNEL) and ultrastructural analysis — is abnormally frequent in the sperm cells of the ejaculate of sterile men with classical biochemical and ultrastructural pattern. In this review, we discuss the possible origins of DNA damage in ejaculated human spermatozoa and the consequences of DNA damage if the apoptotic spermatozoa is used for ICSI. Percentages of DNA fragmentation in human ejaculated sperm are correlated with fertilization rates both after FIV and ICSI. Detection of DNA fragmentation in human sperm could provide additional information about the biochemical integrity of sperm and may be used in future studies for fertilization failures not explained by conventional sperm parameters. However, the analysis of other molecular markers of apoptosis (Fas, Annexine V ...) is necessary to assess the role of apoptosis in human ejaculated sperm cells.     

Endoderm development: from patterning to organogenesis

Although the ectoderm and mesoderm have been the focus of intensive work in the recent era of studies on the molecular control of vertebrate development, the endoderm has received less attention. Because signaling must occur between germ layers in order to achieve a properly organized body, our understanding of the coordinated development of all organs requires a more thorough consideration of the endoderm and its derivatives. This review focuses on present knowledge and perspectives concerning endoderm patterning and organogenesis. Some of the classical embryology of the endoderm is discussed and the progress and deficiencies in cellular and molecular studies are noted.     

Are desmosomes more than tethers for intermediate filaments?

Desmosomes are intercellular adhesive junctions that anchor intermediate filaments at membrane-associated plaques in adjoining cells, thereby forming a three-dimensional supracellular scaffolding that provides tissues with mechanical strength. But desmosomes have also recently been recognized as sensors that respond to environmental and cellular cues by modulating their assembly state and, possibly, their signalling functions.     

Sclerotome development and morphogenesis: when experimental embryology meets genetics

The vertebra develops from the ventral part of the somite, the sclerotome. Sclerotome progenitors are subject to multiple signaling molecules secreted by the adjacent tissues that control their fate. The aim of this article is to discuss the mechanisms of sclerotome induction, chondrogenesis and morphogenesis. By integrating the results from classical studies and recent molecular advances, this will illustrate how the powerful combination of experimental embryology and genetic approaches has recently illuminated the multiple steps of vertebra formation.     

A Multilevel Probabilistic Beam Search Algorithm for the Shortest Common Supersequence Problem

The shortest common supersequence problem is a classical problem with many applications in different fields such as planning, Artificial Intelligence and especially in Bioinformatics. Due to its NP-hardness, we can not expect to efficiently solve this problem using conventional exact techniques. This paper presents a heuristic to tackle this problem based on the use at different levels of a probabilistic variant of a classical heuristic known as Beam Search. The proposed algorithm is empirically analysed and compared to current approaches in the literature. Experiments show that it provides better quality solutions in a reasonable time for medium and large instances of the problem. For very large instances, our heuristic also provides better solutions, but required execution times may increase considerably.     

From field to gel blot: teaching a holistic view of developmental phenomena to undergraduate biology students at the University of Tokyo

We present here an outline of the lectures and laboratory exercises for undergraduate developmental biology students at the University of Tokyo. The main aim of our course is to help students fill the gap between natural history, classical embryology and molecular developmental biology. To achieve this aim, we take up various topics in the lectures, from fertilization and early development to developmental engineering. Our laboratory exercises begin with an introduction to the natural history of the organism. The entire class and the instructors collect newts in the field and discuss features of their mating behavior and so on. In the laboratory, students are absorbed by exercises such as a lampbrush chromosome preparation and an in vitro beating heart induction. After that, students choose their own research projects for which they will employ both classical embryological and modern molecular biological techniques. At the end of our course, the connectivity principle from field to gel blot will be part of the students' understanding.