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

Conrad Hal Waddington's "Experiments on Embryonic Induction III," published in 1934 in the Journal of Experimental Biology, describes the discovery that the primitive streak induces the mammalian embryo. Waddington's hypothesis was that a transplanted primitive streak could induce neural tissue in the ectoderm of the rabbit embryo. The primitive streak defines the axis of an embryo and is capable of inducing the differentiation of various tissues in a developing embryo during gastrulation. In this experiment Waddington was, in fact, able to induce neural differentiation. Waddington noted that the tissue is "competent"; for a chick organizer, and by deduction a mammalian organizer must exist. Competence refers to a cell's ability to respond to an inducing signal, which is temporally limited to certain developmental stages. Waddington's initial work laid the foundation for many decades of research to follow, including further experiments by Waddington with the mammalian organizer.

Samuel Randall Detwiler was an embryologist who studied neural development in embryos and vertebrate retinas. He discovered evidence for the relationship between somites and spinal ganglia, that transplanted limbs can be controlled by foreign ganglia, and the plasticity of ganglia in response to limb transplantations. He also extensively studied vertebrate retinas during and after embryonic development. Detwiler's work established many principles studied in later limb transplantation experiments and was identified by Viktor Hamburger as an important bridge between his and Ross Granville Harrison's research.

Edward B. Lewis studied embryonic development in Drosophila, including the discovery of the cis-trans test for recessive genes, and the identification of the bithorax complex and its role in development in Drosophila. He shared the 1995 Nobel Prize in Physiology or Medicine with Christiane Nüsslein-Volhard and Eric F. Wieschaus for work on genetic control of early embryonic development.

Stanley Cohen is a biochemist who participated in the discovery of nerve growth factor (NGF) and epidermal growth factor (EGF). He shared the 1986 Nobel Prize in Physiology or Medicine with Rita Levi-Montalcini for their work on the discovery of growth factors. His work led to the discovery of many other growth factors and their roles in development.

Conrad Hal Waddington was an embryologist and theoretical biologist. His early experimental work investigated aspects of embryonic induction and the properties of the organizer first identified by Hans Spemann and Hilde Mangold, while his later studies focused on genetic assimilation. Waddington is probably best known for developing the concept of the epigenetic landscape, and he also held significant interest in many different areas ranging from the visual arts and poetry to philosophy. Throughout his career, Waddington maintained that the arts were integral to science, and he continued to draw inspiration from the arts for his own work.

'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.

Conrad Hal Waddington's Organisers and Genes, published in 1940, is a summary of available research and theoretical framework for many concepts related to tissue differentiation in the developing embryo. The book is composed of two main conceptual sections. The first section explores the action and nature of the organizer, while the second section delves into genes and their influence on development.

In his 1907 paper, "Experiments in Transplanting Limbs and Their Bearing Upon the Problems of the Development of Nerves," in the Journal of Experimental Zoology that he edited, Ross Granville Harrison tested the development of nerves in transplanted tissue. He studied neural development by examining two competing theories. Victor Hensen proposed a syncytial theory as a way to explain neural development, suggesting that all the nerves of an embryo were connected directly by cytoplasm laid down early in development, and leaving no room for later modification. Santiago Ramón y Cajal proposed a competing outgrowth theory that nerves develop from the central nervous system, pushing through tissues by growing nerve fibers and growth cones. Harrison's experiment refuted many of the claims of the syncytial theory although it did not produce evidence that could directly prove the outgrowth theory.