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J Gerhart

Publications and source records attributed to J Gerhart.

At least 19 recordsLinked to original sources
PubMed2001

MyoD-positive myoblasts are present in mature fetal organs lacking skeletal muscle.

The epiblast of the chick embryo gives rise to the ectoderm, mesoderm, and endoderm during gastrulation. Previous studies revealed that MyoD-positive cells were present throughout the epiblast, suggesting that skeletal muscle precursors would become incorporated into all three germ layers. The focus of the present study was to examine a variety of organs from the chicken fetus for the presence of myogenic cells. RT-PCR and in situ hybridizations demonstrated that MyoD-positive cells were present in the brain, lung, intestine, kidney, spleen, heart, and liver. When these organs were dissociated and placed in culture, a subpopulation of cells differentiated into skeletal muscle. The G8 antibody was used to label those cells that expressed MyoD in vivo and to follow their fate in vitro. Most, if not all, of the muscle that formed in culture arose from cells that expressed MyoD and G8 in vivo. Practically all of the G8-positive cells from the intestine differentiated after purification by FACS. This population of ectopically located cells appears to be distinct from multipotential stem cells and myofibroblasts. They closely resemble quiescent, stably programmed skeletal myoblasts with the capacity to differentiate when placed in a permissive environment.

Animals↗
PubMed2001

Evolution of the organizer and the chordate body plan.

The discovery of the organizer by Spemann and Mangold in 1924 raised two kinds of questions: those about the means of patterning the chordate body axis and those about the mechanisms of cell determination by induction. Some researchers, stressing the second, have suggested over the years that the organizer is poorly named and doesn't really organize because inducers act permissively, because they are not unique to the organizer, and because multipotent responsive cells develop complex local differentiations under artificial conditions. Furthermore, with the discovery of meso-endoderm induction in 1969, the possibility arose that this earlier induction generates as much organization as, or more than, does the organizer itself. Evidence is summarized in this article that the organizer does fulfill its title with regard to pattern formation: it adds greatly to embryonic organization by providing information about time, place, scale, and orientation for development by nearby members of the large multipotent competence groups surrounding the organizer. Embryos having smaller or larger organizers due to experimental intervention develop defective axial organization. Without an organizer the embryo develops no body axis and none of the four chordate characters: the notochord, gill slits, dorsal hollow nerve chord, and post-anal tail. For normal axis formation, the organizer's tripartite organization is needed. Each part differs in inducers, morphogenesis, and self-differentiation. The organizer is a trait of development of all members of the chordate phylum. In comparison to hemichordates, which constitute a phylum with some similarities to chordates, the chordamesoderm part is unique to the chordate organizer (the trunk-tail organizer). Its convergent extension displaces the gastrula posterior pole from alignment with the animal-vegetal axis and generates a new anteroposterior axis orthogonal to this old one. Once it has extended to full length, its signaling modifies the dorsoventral dimension. This addition to the organizer is seen as a major event in chordate evolution, bringing body organization beyond that achieved by oocyte organization and meso-endoderm induction in other groups.

Animals↗
PubMed2000

DNA dendrimers localize MyoD mRNA in presomitic tissues of the chick embryo.

MyoD expression is thought to be induced in somites in response to factors released by surrounding tissues; however, reverse transcription-PCR and cell culture analyses indicate that myogenic cells are present in the embryo before somite formation. Fluorescently labeled DNA dendrimers were used to identify MyoD expressing cells in presomitic tissues in vivo. Subpopulations of MyoD positive cells were found in the segmental plate, epiblast, mesoderm, and hypoblast. Directly after laying, the epiblast of the two layered embryo contained approximately 20 MyoD positive cells. These results demonstrate that dendrimers are precise and sensitive reagents for localizing low levels of mRNA in tissue sections and whole embryos, and that cells with myogenic potential are present in the embryo before the initiation of gastrulation.

Animals↗
PubMed2000

Inversion of the chordate body axis: are there alternatives?

One major morphological difference between chordates and annelids or arthropods is the opposite orientation of the nerve cord and heart. A long-standing proposal is that the chordate axis evolved by inverting the body of an ancestor with the annelid/arthropod orientation. However, the data can also be explained by a common ancestor with diffuse dorsoventral organization, followed by oppositely directed condensation of the nerve cord and relocation of the heart in the two lines.

Animals↗
PubMed1999

Hepatocyte growth factor/scatter factor promotes a switch from E- to N-cadherin in chick embryo epiblast cells.

Epiblast cells downregulate E-cadherin and upregulate N-cadherin as they ingress through the primitive streak and when placed in culture. The factors that promote the alteration in cadherin expression during gastrulation are unknown. The effects of hepatocyte growth factor/scatter factor (HGF/SF) on cadherin expression were tested in cultures of prestreak epiblast cells. HGF/SF decreased the expression of E-cadherin and increased the percentage of cells with N-cadherin and sarcomeric myosin. Cells with N-cadherin but not E-cadherin differentiated into skeletal muscle. HGF/SF also stimulated proliferation and the formation of cellular aggregates. Sensitivity to HGF/SF in vitro depended on the original position of cells within the epiblast. More cells from the lateral epiblast switched cadherins and proliferated in response to HGF/SF than medial epiblast cells. HGF/SF may affect gastrulation by altering cadherin expression, modulating cell adhesion, and stimulating proliferation within the epiblast.

Animals↗
PubMed1999

1998 Warkany lecture: signaling pathways in development.

Cell-cell signaling pervades all aspects of development, not just in vertebrates, but in all animals (metazoa). It is a typifying characteristic of the major multicellular life forms, animals, plants, and fungi, which diverged about 1.2 billion years ago from a common ancestor descended from a lineage of unicellular life forms. In metazoa, at least 17 kinds of signal transduction pathways operate, each distinguished by its transduction intermediates. Five kinds predominate in early embryonic development, namely, the Wnt, TGF-beta, Hedgehog, RTK, and Notch pathways. Five more are used in late development, and seven more in the functions of differentiated cells. The pathways must have evolved and become conserved in pre-Cambrian times before the divergence of basal members of most of the modern phyla. In metazoan development and physiology, the responses of cells to intercellular signals include cell proliferation, secretion, motility, and transcription. These responses tend to be conserved among metazoa and shared with unicellular eukaryotes and in some cases even with unicellular prokaryotes. Protein components of the responses date back 2 billion years to ancestral eukaryotes or 3 billion to ancestral prokaryotes. Each metazoan developmental process consists of a network of signals and responses, and many of these networks are conserved among metazoa, for example, by insects and mammals. The study of model organisms, even of nonvertebrate groups, is expected to continue to contribute greatly to the understanding of mammalian development and to offer opportunities to analyze the effects of toxicants on development, as well as opportunities to devise incisive assays for toxicants.

Animals↗
PubMed1999

Pieter Nieuwkoop's contributions to the understanding of meso-endoderm induction and neural induction in chordate development.

Pieter Nieuwkoop, who died September 18, 1996, at age 79 in Utrecht, The Netherlands, is remembered by developmental biologists for his numerous research contributions and integrative hypotheses over the past 50 years, especially in the areas of neural induction, meso-endoderm induction, and germ cell induction in chordates. Most of his experimentation was done on the embryos of amphibia, the preferred vertebrate embryo of the early years of the 20th century. One of his last publications contains a comparison of the experimental advantages and disadvantages of anuran and urodele amphibians (Nieuwkoop, 1996). The significance of his findings and interpretations for developmental biology can be estimated from the fact that researchers of many laboratories worldwide continue to work on the phenomena he first described and to extend the hypotheses he first formulated. The aim of this article is to review Nieuwkoop's main contributions and to cite the recent extensions by others.

Animals↗
PubMed1998

Evolvability.

Evolvability is an organism's capacity to generate heritable phenotypic variation. Metazoan evolution is marked by great morphological and physiological diversification, although the core genetic, cell biological, and developmental processes are largely conserved. Metazoan diversification has entailed the evolution of various regulatory processes controlling the time, place, and conditions of use of the conserved core processes. These regulatory processes, and certain of the core processes, have special properties relevant to evolutionary change. The properties of versatile protein elements, weak linkage, compartmentation, redundancy, and exploratory behavior reduce the interdependence of components and confer robustness and flexibility on processes during embryonic development and in adult physiology. They also confer evolvability on the organism by reducing constraints on change and allowing the accumulation of nonlethal variation. Evolvability may have been generally selected in the course of selection for robust, flexible processes suitable for complex development and physiology and specifically selected in lineages undergoing repeated radiations.

Animals↗
PubMed1998

The role of stably committed and uncommitted cells in establishing tissues of the somite.

Somites are blocks of embryonic mesoderm tissue that give rise to skeletal muscle, cartilage, and other connective tissues. The development of different tissues within the somite is influenced by adjacent structures, in particular, the neural tube and notochord. Results of experiments performed in vivo and in vitro suggest that somites contain populations of cells stably programmed to undergo either skeletal myogenesis or chondrogenesis and a population uncommitted to either pathway. The fate of the uncommitted cells would depend on a transfer of information from the committed cells. Communication between committed and uncommitted cells is regulated by cell and tissue interactions that either activate or inhibit this process.

Animals↗
PubMed1997

N-cadherin promotes the commitment and differentiation of skeletal muscle precursor cells.

Cells with the potential to form skeletal muscle are present in the chick embryo prior to gastrulation. Muscle differentiation begins after gastrulation within the somites. The role of cadherin-mediated adhesion in the commitment and differentiation of skeletal muscle precursor cells was examined by analyzing the expression of cell-cell adhesion molecules in cultures of epiblast, segmental plate, and somite cells and by determining the effects of adhesion-perturbing antibodies on the accumulation of MyoD and sarcomeric myosin. Cultured primitive streak stage epiblast cells downregulate E-cadherin and upregulate N-cadherin. This switch in cadherin expression also occurs in vivo as epiblast cells enter the primitive streak. Although MyoD protein is present in cells with N- or E-cadherin, only cells with N-cadherin differentiate into skeletal muscle. In contrast to the primitive streak stage epiblast cells, prestreak epiblast cells maintain the expression of E-cadherin in vitro. While the majority of prestreak cells contain MyoD, only a few synthesize myosin. Treatment of primitive streak stage epiblast cells with function-perturbing antibodies to N-cadherin resulted in an inhibition of myosin accumulation and a decrease in the percentage of cells with MyoD. Segmental plate and somite cells are similar to primitive streak stage epiblast cells in that most differentiated into skeletal muscle when cultured in serum-free medium. While function-perturbing antibodies to N-cadherin inhibited the accumulation of myosin in these mesoderm cells, the number of MyoD positive cells was unaffected in somite cultures and only partially reduced in segmental plate cultures. These results suggest that N-cadherin-mediated cell-cell adhesion is involved in both the commitment of muscle precursors and their terminal differentiation.

Animals↗
PubMed1997

Formation and function of Spemann's organizer.

The organizer is formed in an equatorial sector of the blastula stage amphibian embryo by cells that have responded to two maternal agents: a general mesoendoderm inducer (involving the TFG-beta signaling pathway) and a dorsal modifier (probably involving the Wnt signaling pathway). The meso-endoderm inducer is secreted by most vegetal cells, those containing maternal materials that had been localized in the vegetal hemisphere of the oocyte during oogenesis. As a consequence of the inducer's distribution and action, the competence domains of prospective ectoderm, mesoderm, and endoderm are established in an animal-to-vegetal order in the blastula. The dorsal modifier signal is secreted by a sector of cells of the animal and vegetal hemispheres on one side of the blastula. These cells contain maternal materials transported there in the first cell cycle from the vegetal pole of the egg along microtubules aligned by cortical rotation. The Nieuwkoop center is the region of blastula cells secreting both maternal signals, and hence specifying the organizer in an equatorial sector. Final steps of organizer formation at the late blastula or early gastrula stage may involve locally secreted zygotic signals as well. At the gastrula stage, the organizer secretes a variety of zygotic proteins that act as antagonists to various members of the BMP and Wnt families of ligands, which are secreted by cells of the competence domains surrounding the organizer. BMPs and Wnts favor ventral development, and cells near the organizer are protected from these agents by the organizer's inducers. The nearby cells are derepressed in their inherent capacity for dorsal development, which is apparent in the neural induction of the ectoderm, dorsalization of the mesoderm, and anteriorization of the endoderm. The organizer also engages in extensive specialized morphogenesis, which brings it within range of responsive cell groups. It also self-differentiates to a variety of axial tissues of the body.

Amphibians↗
PubMed1996

Skeletal myogenesis: the preferred pathway of chick embryo epiblast cells in vitro.

The epiblast layer of the chick embryo gives rise to all embryonic tissues. In vitro analyses were carried out to determine whether epiblast cells could form skeletal muscle prior to entry into the primitive streak. Epiblasts were separated from the mesoderm, hypoblast, and primitive streak, dissociated to produce a single cell suspension, and plated at high density. Myogenesis began on the first day in culture, and by the fifth day most cells had differentiated into skeletal muscle. Some cells differentiated without replicating. MyoD messenger RNA was present in epiblast tissue and translated in practically all cells in culture. Cells from regions of the epiblast which do not form muscle later in the embryo did so in vitro. Epiblasts cultured for 2 days as an intact epithelium, or in the presence of the mesoderm and hypoblast, did not undergo myogenesis. These findings demonstrate that myogenic potential is wide-spread within the primitive streak stage epiblast, and that muscle differentiation, which occurs relatively autonomously in culture, can be prevented by cell and tissue interactions.

Animals↗