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PubMed1999

The neural induction process; its morphogenetic aspects.

This posthumous review of early embryonic inductions concludes: 1) the amphibian egg has only two distinct components, animal and vegetal. Interactions at their mutual boundary forms meso-endoderm. This is "meso-endoderm induction", not just "mesoderm induction". 2) The dorso-ventral polarity of the yolk mass implies a dorsally situated inducing centre. 3) Accumulation of cells into one, two, three or many cell masses [problastopores] along the circumference of the meso-endoderm results in as many axes, implying a self-organizing capacity of meso-endoderm. 4) Induction of the meso-endoderm is slow, spreading cell to cell through the animal moiety from the boundary of the vegetal yolk mass towards the animal pole. 5) Interaction between mesoderm and ectoderm is a separate step leading to cranio-caudal differentiation of the archenteron roof. 6) The initial invaginating endoderm and mesoderm, representing the future pharynx endoderm and prechordal plate mesoderm, first contacts the most posterior presumptive neurectoderm after having passed the still uninvaginated trunk mesoderm. At that moment an antero-posterior level neural induction actually starts. 7) The ectoderm contraction wave coincides spatially and temporally with the induced neural plate. 8) Two successive homoiogenetic waves of inductive activity pass through the presumptive neurectoderm in the anterior direction, the first one, "activation", giving rise to neural differentiation and ultimately forebrain, the second one, "transformation", to more caudal CNS structures. These are separate, successive steps in CNS regional induction. 9) The midbrain represents a secondary formation in the neural plate. 10) The observed changes in morphogenesis may depend upon separate, successive binary decisions via [cell and] nuclear state splitters [involving differentiation waves].

Ambystoma↗
PubMed1975

Epithelio-mesenchymal interface during mouse kidney tubule induction in vivo.

Transmission and scanning electron microscopy were used to study the epithelio-mesenchymal interface between the interacting mouse ureter-bud and the metanephric mesenchyme. The gap between the epithelial and mesenchymal cells varied in width. At the stalk of the ureter-bud the interspace was often about 1 mum, but in the inductively active areas at the tips of the branching ureter-bud epithelio-mesenchymal contacts were seen through discontinuities in the basal lamina. At these points the gap between the interacting cells was often less than 20 nm, in places less than 10 nm. The amount of electron-dense, ruthenium-red-positive material was greatest at the stalk of the ureter-bud, but only a small amount of extracellular material was found between the interacting cells at the tips. Whether epithelio-mesenchymal cell contacts play a role in kidney tubule induction is not yet known, but their existence in the inductively active areas and their absence in inactive zones suggests that they are morphogenetically significant. The finding also obviates the need to postulate long-range transmission of inductive signals to explain this example of embryonic induction.

Animals↗
PubMed1995

Fate maps of the zebrafish embryo.

In the past few years, we have seen a surge of interest in the zebrafish as a model system for the study of embryonic induction and patterning. This review summarizes our current knowledge of the organization of zebrafish fate maps during early development. Recent advances have addressed the relationship between early cleavage planes and the future dorsal axis, the pattern of cell mixing during blastula and gastrula stages, and the morphogenesis of the trunk neural keel. In addition, refined fate maps have become available for the embryonic shield, the central nervous system, and the heart. In combination with recent advances in molecular and genetic manipulations, these fate maps set the stage for new, more incisive, experimental approaches.

Animals↗
PubMed1991

Pathogenesis of benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia (BPH) remains largely unresolved. Three major theories have evolved over the years, each emphasizing a possible causative mechanism. The first theory, the dihydrotestosterone hypothesis, is based on the failure of BPH to develop in men castrated prior to puberty. The second, the embryonic reawakening theory, assumes a reawakening of the embryonic induction potential of prostatic stroma. The third, or stem cell theory, postulates the development of BPH through an increase in the number of stem cells or through an abnormal increase in clonal expansion of amplifying or transit cells. These mechanisms may act in concert.

Androgens↗
PubMed1996

Factors responsible for the establishment of the body plan in the amphibian embryo.

A central topic of embryology is the establishment of the body plan during embryogenesis. Starting with maternal factors distributed in the early cleavage stages in distinct patterns and gradients cell-to-cell interactions including early embryonic induction result in the formation of mesoderm and the organizer area. While many facts are known about the role of growth factors like activin (closely related to the vegetalizing factor), processed Vg1, BMPs and FGF for mesoderm formation, the establishment of the central nervous system is not yet well understood. However, there is growing evidence that neural induction is a multistep process at the level of the dorsal mesoderm (organizer) and the reacting neuroectoderm. Therefore the existence of only one neuralizing factor is unlikely. We report about data that follistatin protein is not a direct neural inducer. Furthermore our comparative studies of Xenopus and Triturus exogastrulae indicate that planar signals are unlikely in the Triturus embryo (urodeles) during the early steps of neural induction. Vertical signals emanating from the chordamesoderm are essential for the terminal neuralization and regionalization of the central nervous system during gastrulation for both Xenopus and Triturus. The putative role of neuralizing factors and BMP/activin-like molecules for the stabilization or shift of neuroectoderm into different pathways of differentiation (epidermis or neural default state) is discussed.

Amphibians↗
PubMed1999

Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation.

Embryonic metanephroi, differentiating into the adult kidney, have come to be a generally accepted model system for organogenesis. Nephrogenesis implies a highly controlled series of morphogenetic and differentiation events that starts with reciprocal inductive interactions between two different primordial tissues and leads, in one of two mainstream processes, to the formation of mesenchymal condensations and aggregates. These go through the intricate process of mesenchyme-to-epithelium transition by which epithelial cell polarization is initiated, and they continue to differentiate into the highly specialized epithelial cell populations of the nephron. Each step along the developmental metanephrogenic pathway is initiated and organized by signaling molecules that are locally secreted polypeptides encoded by different gene families and regulated by transcription factors. Nephrogenesis proceeds from the deep to the outer cortex, and it is directed by a second, entirely different developmental process, the ductal branching of the ureteric bud-derived collecting tubule. Both systems, the nephrogenic (mesenchymal) and the ductogenic (ureteric), undergo a repeat series of inductive signaling that serves to organize the architecture and differentiated cell functions in a cascade of developmental gene programs. The aim of this review is to present a coherent picture of principles and mechanisms in embryonic renal epithelia.

Animals↗
PubMed1994

Growth factors in development: the role of TGF-beta related polypeptide signalling molecules in embryogenesis.

Embryonic induction, the process by which signals from one cell population influence the fate of another, plays an essential role in the development of all organisms so far studied. In many cases, the signalling molecules belong to large families of highly conserved proteins, originally identified as mammalian growth factors. The largest known family is related to Transforming Growth Factor-beta (TGF-beta) and currently consists of at least 24 different members. Genetic studies in Drosophila on the TGF-beta related gene, decapentaplegic (dpp), reveal the existence of conserved mechanisms regulating both the expression of the protein during development and the way in which it interacts with other signalling molecules to generate pattern within embryonic tissues. Comparative studies on another TGF-beta related gene, known as Bone Morphogenetic Protein-4 (BMP-4), in Xenopus and mouse point to a conserved role in specifying posteroventral mesoderm during gastrulation. Analysis of other polypeptide signalling molecules during gastrulation suggests that their interaction in the generation of the overall body plan has also been conserved during vertebrate evolution.

Animals↗
PubMed1981

Positional information and pattern formation.

Spatial patterns of cellular differentiation may arise from cells first being assigned a position, as in a coordinate system, and then interpreting the positional value that they have acquired. This interpretation will depend on their genetic constitution and developmental history. Different patterns may thus arise from similar positional fields. The specification of positional value may involve a positional signal, such as the concentration of a diffusible morphogen, but can also depend on how long the cells remain in a particular region, such as a progress zone. Positional values may also be acquired by direct transfer from one cell layer to another, as in directed embryonic induction. Positional value, unlike a positional signal, involves long-term memory, and can be regarded as a type of cell determination. Cells of the same differentiation class may have different positional values and may thus be non-equivalent. Evidence is presented for a signal providing positional information along the antero-posterior axis during chick limb development. This signal has properties similar to those of a diffusible morphogen.

Animals↗
PubMed1998

Intercellular interactions as a basis for the expedient behaviour of multicellular systems.

Functional and structural aspects of intercellular interactions are considered. Chemical substances are universal mediators of intercellular interactions. Electrical and mechanical interactions are also involved in cell-cell cooperation. Functional peculiarities of the two principal types of intercellular interactions-ligand-receptor interactions and interactions based on permeable contacts-are compared. Examples of basic tissue processes are given (such as the mechanisms of embryonic induction and differentiation, regulation of cell proliferation, temporal and spatial regulation of the activity of differentiated cells, interactions between excitable cells) to illustrate the notion that the types of intercellular interactions are mutually complementary and fulfill different functions. Ligand-receptor interactions predominantly provide signal functions and ensure intertissue interactions, while the interactions based on permeable contacts mainly fulfill intratissue coordination relying on positional information and the exchange of energy and matter.

Cell Communication↗
PubMed1984

Is a bi-clonal interaction, analogous to that underlying embryogenesis the origin of the earliest malignant phenotype?

We propose a theoretical model of carcinogenesis which parallels embryonic induction. It is based on the interaction between two clones of cells. One of them is of germ cell ancestry and is the source of transforming effector cells. The second clone is the potential target of such travelling "lymphocytoid" cells and emerges in tissues exhibiting the precancerous picture of dysplasia. In atypical fields each endopolyploid cell, arrested in G2 and involved in genomic changes, is the stem of a clonal growth. This emerging new phenotype is subjected to policing control by wandering effector cells. This situation establishes the probability of a random collision between two cells pertaining to different lineages, with two possible antithetical results, cytolysis or cell fusion comparable to fertilization. The latter event is suggested to determine malignancy.

Animals↗
PubMed1999

Initiation of mammalian liver development from endoderm by fibroblast growth factors.

The signaling molecules that elicit embryonic induction of the liver from the mammalian gut endoderm or induction of other gut-derived organs are unknown. Close proximity of cardiac mesoderm, which expresses fibroblast growth factors (FGFs) 1, 2, and 8, causes the foregut endoderm to develop into the liver. Treatment of isolated foregut endoderm from mouse embryos with FGF1 or FGF2, but not FGF8, was sufficient to replace cardiac mesoderm as an inducer of the liver gene expression program, the latter being the first step of hepatogenesis. The hepatogenic response was restricted to endoderm tissue, which selectively coexpresses FGF receptors 1 and 4. Further studies with FGFs and their specific inhibitors showed that FGF8 contributes to the morphogenetic outgrowth of the hepatic endoderm. Thus, different FGF signals appear to initiate distinct phases of liver development during mammalian organogenesis.

Animals↗
PubMed2001

Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice.

Embryonic induction of hair follicles is a fascinating model of localized morphogenesis from a simple homogeneous epithelial cell sheet. Accumulating evidence indicates that Sonic hedgehog (Shh) signaling plays a central role in hair follicle formation. We quantitated the expression levels of Shh and its receptor genes, Patched (Ptc) and Patched-2 (Ptch2), in two distinct experimental systems in which the development of hair follicles was suppressed. Shh, Ptc, and Ptch2 were induced about six- to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture. This induction was almost completely inhibited both in the developing skin tissue of ICR mice cultured with 30ng/ml epidermal growth factor and in embryos of Tabby mutant mice (a model of hypohidrotic ectodermal dysplasia) at 14.5-15.5 days postcoitus. Expression of Shh, Ptc and Ptch2 was induced in the Tabby embryos at 16.5 days postcoitus, indicating that Shh signaling may be involved in the formation not only of the well-studied guard hair but also of the awl hair. The potential of the two biological systems for studying molecular mechanisms in hair follicle formation, particularly at an early phase including Shh signaling, is discussed.

Animals↗
PubMed1997

A member of the Met/HGF-receptor family is expressed in a BMP-4-like pattern in the ectoderm of Xenopus gastrulae.

The importance and involvement of growth factors and their corresponding receptors in embryonic induction has been more and more recognized during the past decade, in particular by loss-of-function experiments using dominant negative receptors. Here, we report the isolation of XHR, a Xenopus receptor-type tyrosine kinase, with homology to members of the Met/hepatocyte growth factor (HGF)-receptor family. Sequence comparison of XHR with other members of the Met/HGF-receptor family as well as in situ expression analyses suggest that XHR represents a novel member of this family of receptor-type tyrosine kinases. As could be shown by whole-mount in situ analysis, XHR transcripts are first expressed in the entire ectoderm at the onset of gastrulation. As gastrulation proceeds, XHR-transcription is turned off in cells induced by dorsal mesoderm to form neural tissue and thus, becomes predominantly confined to prospective epidermis. The strikingly similar expression patterns of XHR and Bone Morphogenetic Protein-4 (BMP-4), an inducer of epidermis and inhibitor of neural development, suggest an involvement of XHR signalling in the early cell-fate decision of ectodermal cells to form either neural derivatives or epidermis.

Animals↗
PubMed1992

Mesoderm induction and development of the embryonic axis in amniotes.

The mechanisms controlling the formation of the embryonic axis, and specifically those that give rise to the mesoderm, have received renewed attention recently. In the frog, some of these mechanisms have begun to be elucidated, and several factors have been found to cause uncommitted ectoderm cells to differentiate into mesoderm. All of the factors identified to date are related either to fibroblast growth factor (FGF) or to transforming growth factor beta (TGF-beta). Do the mechanisms that generate the embryonic axis of amphibians also operate in chick and mouse embryos? Here I address how amphibian and amniote embryos might provide complementary pieces of a puzzle.

Amphibians↗
PubMed2002

Inductive patterning of the embryonic brain in Drosophila.

In vertebrates (deuterostomes), brain patterning depends on signals from adjacent tissues. For example, holoprosencephaly, the most common brain anomaly in humans, results from defects in signaling between the embryonic prechordal plate (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have examined whether a similar mechanism of brain development occurs in the protostome Drosophila, and find that the foregut and mesoderm act to pattern the fly embryonic brain. When the foregut and mesoderm of Drosophila are ablated, brain patterning is disrupted. The loss of Hedgehog expressed in the foregut appears to mediate this effect, as it does in vertebrates. One mechanism whereby these defects occur is a disruption of normal apoptosis in the brain. These data argue that the last common ancestor of protostomes and deuterostomes had a prototype of the brains present in modern animals, and also suggest that the foregut and mesoderm contributed to the patterning of this 'proto-brain'. They also argue that the foreguts of protostomes and deuterostomes, which have traditionally been assigned to different germ layers, are actually homologous.

Animals↗
PubMed1978

[Isolation and ways of acting of morphogenetic factors during early embryogenesis].

The attempts at isolation and characterization of the factors mediating the embryonic induction are summarized. A method is described in detail which allowed to isolate the purified form from the mixtures of chick embryonic tissues a vegetalizing protein factor which induces the mesoderm and endoderm in the ectoderm of amphibian gastrulae. Besides, its inhibitor was isolated which is also a protein; the inhibitors supposedly block the action of the most inducing factors but one or some of them. The isolation of the inducing factor in the pure form allowed to reinvestigate with the greatest precision the problem whether the induction is mediated by the contact of cell surfaces or the penetration of substances in the reacting cells and to show that the inducing factor penetrates in the cells upon the induction in the gastrula ectoderm. The effect of cyclic monophosphates and changes in potassium and sodium intracellular concentration as factors participating in the induction was also tested and it was shown that neither of these factors, contrary to the expectations, led to he induction phenomena. The importance of the vegetalizing factor concentration for the segregation of the primary ectodermal zone into ectodermal and mesodermal and, secondarily, nerve cellis discussed.

Animals↗
PubMed2006

Human development VI: supracellular morphogenesis. The origin of biological and cellular order.

Uninterrupted morphogenesis shows the informational potentials of biological organisms. Experimentally disturbed morphogenesis shows the compensational dynamics of the biological informational system, which is the rich informational redundancy. In this paper, we use these data to describe morphogenesis in terms of the development of supracellular levels of the organism, and we define complex epigenesis and supracellular differentiation. We review the phenomena of regeneration and induction of Hydra and amphibians, and the higher animal's informational needs for developing their complex nervous systems. We argue, also building on the NO-GO theorem for ontogenesis as chemistry, that the traditional chemical explanations of high-level informational events in ontogenesis, such as transmutation, regeneration, and induction, are insufficient. We analyze the informational dynamics of three embryonic compensatory reactions to different types of disturbances: (1) transmutations of the imaginal discs of insects, (2) regeneration after removal of embryonic tissue, and (3) embryonic induction, where two tissues that normally are separated experimentally are made to influence each other. We describe morphogenesis as a complex bifurcation, and the resulting morphological levels of the organism as organized in a fractal manner and supported by positional information. We suggest that some kind of real nonchemical phenomenon must be taking form in living organisms as an information-carrying dynamic fractal field, causing morhogenesis and supporting the organism's morphology through time. We argue that only such a phenomenon that provides information-directed self-organization to the organism is able to explain the observed dynamic distribution of biological information through morphogenesis and the organism's ability to rejuvenate and heal.

Cell Physiological Phenomena↗
PubMed1988

Xenopus laevis in developmental and molecular biology.

Xenopus laevis is a prime system for the study of embryogenesis in vertebrates. Both prelocalized information in the egg and inductive interactions between cells contribute to the ordered increase in complexity during development. Embryonic induction, discovered in amphibians, is being studied intensely in Xenopus; recent work suggests a role for growth factors in this process. Contributions of the Xenopus system to the analysis of ribosomal and 5S RNA genes, and the diverse and highly productive applications of the oocyte injection technology, are also summarized.

Animals↗