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

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

'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.

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.

Santiago Felipe Ramon y Cajal investigated brains in the nineteenth and twentieth centuries in Spain. He identified and individuated many components of the brain, including the neuron and the axon. He used chick embryos instead of adult animals, then customary in brain research, to study the development and physiology of the cerebellum, spinal cord, and retina. Ramon y Cajal received the Nobel Prize in Physiology and Medicine in 1906, along with Camillo Golgi, for his work on the structure of the nervous system.

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.

Vitamin A (retinol) is an essential vitamin in the daily functioning of human beings that helps regulate cellular differentiation of epithelial tissue. Studies have shown that an excess of vitamin A can affect embryonic development and result in teratogenesis, or the production of birth defects in a developing embryo. Excess intake of vitamin A and retinoids by pregnant women often results malformations to fetuses' skulls, faces, limbs, eyes, central nervous system. Additionally, doctors often use derivatives of vitamin A, known as retinoids, as medicine to treat a number of skin conditions and carcinomas, the most common form of human cancers.

Dizhou Tong, also called Ti Chou Tung, studied marine animals and helped introduce and organize experimental embryology in China during the twentieth century. He introduced cellular nuclear transfer technology to the Chinese biological community, developed methods to clone organisms from many marine species, and investigated the role of cytoplasm in early development. Tong's administrative and scientific leadership in the fields of marine, cellular, and developmental biology contributed to China's experimental embryology research programs.

In the early 1960s, John W. Saunders Jr., Mary T. Gasseling, and Lilyan C. Saunders in the US investigated how cells die in the developing limbs of chick embryos. They studied when and where in developing limbs many cells die, and they studied the functions of cell death in wing development. At a time when only a few developmental biologists studied cell death, or apoptosis, Saunders and his colleagues showed that researchers could use embryological experiments to uncover the causal mechanisms of apotosis. The researchers published many of their results in the 1962 paper 'Cellular death in morphogenesis of the avian wing.'

Andrew Francis Dixon studied human anatomy and egg cells at the turn of the twentieth century in Ireland and Great Britain. Dixon studied the sensory and motor nervous system of the face, the cancellous bone tissue of the femur, supernumerary kidneys, and the urogenital system. In 1927 Dixon described a mature human ovarian follicle. This follicle, Dixon noted, contained an immature human egg cell (oocyte) with a visible first polar body and the beginnings of the second polar body. Dixon's work helped researchers describe many of the items found in follicles during the production of oocytes, and it helped them identify when, where, and how those items were produced. Based upon his descriptions, later researchers further described polar bodies and investigated their functions.