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

Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty times before they cannot divide any further. Researchers later found that the cause of the Hayflick Limit is the shortening of telomeres, or portions of DNA at the ends of chromosomes that slowly degrade as cells replicate. Hayflick used his research on normal embryonic cells to develop a vaccine for polio, and from HayflickÕs published directions, scientists developed vaccines for rubella, rabies, adenovirus, measles, chickenpox and shingles.

'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.

This diagram shows how NCCs migrate differently in rats, birds and amphibians. The arrows represent both chronology of NCCs migration and the differential paths that NCCs follow in different classes of animals. The solid black portion of each illustration represents the neural crest, and the large black dots in (c) and in (f) represent the neural crest cells. The speckled sections that at first form a basin in (a) and then close to form a tube in (f) represent the neural ectoderm. The solid white portions represent the epidermal ectoderm. During the neurula stage of all vertebrate embryos (a), the neural crest is located in two places on the neural plate. As the neural tube forms (b), a process called neurulation, the neural crest moves with the folding plate as it forms the junction between the neural and epidermal ectoderm. NCCs migrate differently in different classes of vertebrates (c-f). For instance, in rats (c), the NCCs migrate away from the neural crest before neurulation completes and while the neural fold is still open. In birds (d and f), neural crest cells do not migrate until the neural fold closes. In amphibians (e and f), the neural crest cells migrate after neurulation completes, and only after the cells have accumulated above the neural tube. Subsequently, NCCs will all migrate down their specialized pathways and diversify into the several sub-types of NCCs.

Victor Jollos studied fruit flies and microorganisms in Europe and the US, and he introduced the concept of Dauermodifikationen in the early 1900s. The concept of Dauermodifikationen refers to environmentally-induced traits that are heritable for only a limited number of generations. Some scientists interpreted the results of Jollos's work on Paramecium and Drosophila as
evidence for cytoplasmic inheritance. Jollos was forced to emigrate from Germany to the United States due to anti-semitic government policies in the early 1930s. Nevertheless, his work on Dauermodifikationen remained central to theoretical discourse among German zoologists concerning heredity, development, and evolution.

Petr Kropotkin proposed the theory of Pleistocene ice age, alternative theories of evolution based on embryology, and he advocated anarchist and communist social doctrines in Europe during the nineteenth and twentieth centuries. He traveled in eastern Siberia and Manchuria from 1863 until 1867, and his subsequent publications about that area's geography became authoritative until the middle of the twentieth century. Kropotkin argued that his geographic and geologic observations in Asia, Finland, Sweden, and Canada, supported the theory of Pleistocene continental glaciation, often called the ice age. He was one of the first to study the ancient geography and climate of the Quaternary period, which spans from 2.5 million years ago until the present. Around the turn of the nineteenth century, Kropotkin offered what he said were complementary amendments to Charles Darwin's 1859 theory of evolution by natural selection. Kropotkin employed a variety of arguments from natural history, embryology, and geography to support his theory of mutual aid, which he argued was a positive mechanistic addition to the theory of evolution.

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.

Friedrich Tiedemann studied the anatomy of humans and animals in the nineteenth century in Germany. He published on zoological subjects, on the heart of fish, the anatomy of amphibians and echinoderms, and the lymphatic and respiratory system in birds. In addition to his zoological anatomy, Tiedemann, working with the chemist Leopold Gmelin, published about how the digestive system functioned. Towards the end of his career Tiedemann published a comparative anatomy of the brains of white Europeans, black Africans, and Orangutans, in which he argued that there were no appreciable differences between the structure of the brains of blacks, women, and white European men that would suggest they were intellectually different. Tiedemann also researched the embryonic development of the brain and circulatory systems of human fetuses.

Julius von Sachs helped establish plant physiology through his experiments in latter nineteenth-century Germany. Sachs infused the inchoate discipline of plant physiology with experimental techniques and a mechanistic stance, both of which cemented his place as one of the discipline s founders. Sachs trained a generation of plant physiologists, and his stress on experimentation and mechanism influenced biologists in other disciplines, especially embryologist Jacques Loeb.

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.