Embryo Project Encyclopedia

Mechanism of Notch Signaling: The image depicts a type of cell signaling, in which two animal cells interact and transmit a molecular signal from one to the other. The process results in the production of proteins, which influence the cells as they differentiate, move, and contribute to embryological development. In the membrane of the signaling cell, there is a ligand (represented by a green oval). The ligand functions to activate a change in a receptor molecule. In the receiving cell, there are receptors; in this case, Notch proteins (represented by orange forks). The Notch proteins are embedded in the receiving cell membrane, and they have at least two parts: an intracellular domain (inside the cell) and the receptor (outside the cell). Once the ligand and receptor bind to each other, a protease (represented by the dark red triangle) can sever the intracellular domain from the rest of the Notch receptor. Inside the nucleus of the receiving cell (represented by the gray area) are the cellês DNA (represented by the multi-colored helices) and its transcription factors (blue rectangles). Transcription factors are proteins that bind to DNA to regulate transcription, the first step in gene expression, which eventually yields proteins or other products. Initially, repressor proteins (represented by a red irregular hexagon) prevent transcription factors from allowing transcription. When the severed Notch receptor intracellular domain reaches the nucleus, it displaces the repressor. The transcription factor can then signal for transcription to occur. 1) There is a Notch receptor protein in the membrane of a receiving cell, and a ligand for this receptor (for example, Delta) in the membrane of the signaling cell. When the ligand binds to the receptor, the intracellular domain of the receptor changes shape. 2) Inside the receiving cell, there are proteases. Once the intracellular domain of the receptor changes shape, the protease can bind to it and shear the intracellular domain away from the rest of the receptor molecule. 3) The severed intracellular domain is shuttled to the receiving cell nucleus. Here, the intracellular domain displaces a repressor protein. This allows a transcription factor to initiate DNA transcription. During transcription, DNA is used as a template to create RNA. Following transcription, the process of translation occurs, which uses RNA as a template to create proteins. These proteins influence the behavior, fate, and differentiation of cells, which contribute to normal embryonic development

Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.

'On the Permanent Life of Tissues outside of the Organism' reports Alexis Carrel's 1912 experiments on the maintenance of tissue in culture media. At the time, Carrel was a French surgeon and biologist working at the Rockefeller Institute in New York City. In his paper, Carrel reported that he had successfully maintained tissue cultures, which derived from connective tissues of developing chicks and other tissue sources, by serially culturing them. Among all the tissue cultures Carrel reported, one was maintained for more than two months, whereas previous efforts had only been able to keep tissues in vitro for three to fifteen days. Carrel’s experiments contributed to the development of long-term tissue culture techniques, which were useful in the study of embryology and eventually became instrumental in stem cell research. Despite later evidence to the contrary, Carrel believed that as long as the tissue culture method was accurately applied, tissues kept outside of the organisms should be able to divide indefinitely and have permanent life.

Christiane Nusslein-Volhard studied how genes control embryonic development in flies and in fish in Europe during the twentieth and twenty-first centuries. In the 1970s, Nusslein-Volhard focused her career on studying the genetic control of development in the fruit fly Drosophila melanogaster. In 1988, Nusslein-Volhard identified the first described morphogen, a protein coded by the gene bicoid in flies. In 1995, along with Eric F. Wieschaus and Edward B. Lewis, she received the Nobel Prize in Physiology or Medicine for the discovery of genes that establish the body plan and segmentation in Drosophila. Nusslein-Volhard also investigated the genetic control of embryonic development to zebrafish, further generalizing her findings and helping establishing zebrafish as a model organism for studies of vertebrate development.

The Spemann-Mangold organizer, also known as the Spemann organizer, is a cluster of cells in the developing embryo of an amphibian that induces development of the central nervous system. Hilde Mangold was a PhD candidate who conducted the organizer experiment in 1921 under the direction of her graduate advisor, Hans Spemann, at the University of Freiburg in Freiburg, German. The discovery of the Spemann-Mangold organizer introduced the concept of induction in embryonic development. Now integral to the field of developmental biology, induction is the process by which the identity of certain cells influences the developmental fate of surrounding cells. Spemann received the Nobel Prize in Medicine in 1935 for his work in describing the process of induction in amphibians. The Spemann-Mangold organizer drew the attention of embryologists, and it spurred numerous experiments on the nature of induction in many types of developing embryos.

In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.

On 9 August 2001, US President George W. Bush gave an eleven-minute speech from his ranch in Crawford, Texas, on the ethics and fate of federal funding for stem cell research. Bush also announced the creation of a special council to oversee stem cell research. In the speech President Bush acknowledged the importance of issues surrounding stem cell research to many Americans, presented different arguments in favor of and opposing embryonic stem cell research, and explained his decision to limit but not completely eliminate potential federal funding for embryonic stem cell (ESC) research. The speech was important to embryology as a field because it determined the US government's policy on funding human ESC research for the eight years of George W. Bush's administration.

Induced pluripotent stem cells (iPSCs) are studied carefully by scientists not just because they are a potential source of stem cells that circumvents ethical controversy involved with experimentation on human embryos, but also because of their unique potential to advance the field of regenerative medicine. First generated in a lab by Kazutoshi Takahashi and Shinya Yamanaka in 2006, iPSCs have the ability to differentiate into cells of all types. If scientists discover how to induce differentiated cells to return to a pluripotent state using a method that leaves the iPSCs safe for transplantation, then patients could receive stem cell transplants with cells containing their own DNA. This would presumably remove the danger of transplant rejection that comes with foreign cell transplantation.

Shinya Yamanaka gained international prominence after publishing articles detailing the successful generation of induced pluripotent stem (iPS) cells, first in mice, then in humans. Yamanaka induced somatic cells to act like human embryonic stem cells (hESCs), allowing researchers to experiment with non-embryonic stem cells with a similar capacity as hESCs. The research involving iPS cells therefore offered new potential for research and application in medical treatment, without many of the ethical objections that hESC research entailed.

In the July 2007 issue of Nature, Keisuke Okita, Tomoko Ichisaka, and Shinya Yamanaka added to the new work on induced pluripotent stem cells (iPSCs) with their "Generation of Germline-Competent Induced Pluripotent Stem Cells" (henceforth abbreviated "Generation"). The authors begin the paper by noting their desire to find a method for inducing somatic cells of patients to return to a pluripotent state, a state from which the cell can differentiate into any type of tissue but cannot form an entire organism. If this is made possible, the authors claim, the ethical controversy surrounding the use of embryonic stem cells (ES cells) and the dangers of patient rejection of donated ES cells could be bypassed completely.