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

Boris Ephrussi and George Wells Beadle developed a transplantation technique on flies, Drosophila melanogaster, which they described in their 1936 article A Technique of Transplantation for Drosophila. The technique of injecting a tissue from one fly larva into another fly larva, using a micropipette, to grow that tissue in the second larvae, was a means for investigating development of Drosophila. Through this technique, Beadle and Ephrussi studied the role of genes in embryological processes. Beadle and Ephrussi were the first to apply the transplantation method, which had previously been used in the study of larger insects, to the smaller sized Drosophila. Beadle and Ephrussi used this method of transplantation to determine if parts of the optic disc, the section of a larvae that later become the eye buds in the adult, could be extracted from one larva and transplanted into another. They later built upon this research to relate the production of molecules in cells to gene function.

'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.

The one gene-one enzyme hypothesis, proposed by George Wells Beadle in the US in 1941, is the theory that each gene directly produces a single enzyme, which consequently affects an individual step in a metabolic pathway. In 1941, Beadle demonstrated that one gene in a fruit fly controlled a single, specific chemical reaction in the fruit fly, which one enzyme controlled. In the 1950s, the theory that genes produce enzymes that control a single metabolic step was dubbed the one geneÐone enzyme hypothesis by Norman Horowitz, a professor at the California Institute of Technology (Caltech) and an associate of Beadle's. This concept helped researchers characterize genes as chemical molecules, and it helped them identify the functions of those molecules.

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.

George Wells Beadle and Edward Lawrie Tatum's 1941 article Genetic Control of Biochemical Reactions in Neurospora detailed their experiments on how genes regulated chemical reactions, and how the chemical reactions in turn affected development in the organism. Beadle and Tatum experimented on Neurospora, a type of bread mold, and they concluded that mutations to genes affected the enzymes of organisms, a result that biologists later generalized to proteins, not just enzymes. Beadle and Tatum's experiments provided an early link between genetics and the field of molecular biology.

George Wells Beadle studied corn, fruit flies, and funguses in the US during the twentieth century. These studies helped Beadle earn the 1958 Nobel Prize in Physiology or Medicine. Beadle shared the prize with Edward Tatum for their discovery that genes help regulate chemical processes in and between cells. This finding, initially termed the one gene-one enzyme hypothesis, helped scientists develop new techniques to study genes and DNA as molecules, not just as units of heredity between generations of organisms. By inducing mutations in organisms while they were in different embryonic stages, Beadle's work on Drosophila and Neurospora led to the analysis of the cell cycle and embryonic development processes.

St. George Jackson Mivart studied animals and worked in England during the nineteenth century. He also proposed a theory of organismal development that he called individuation, and he critiqued Charles Darwin's argument for evolution by natural selection. His work on prosimians, a group of primates excluding apes and monkeys, helped scientists better investigate the Primate group. In his work On the Genesis of Species, Mivart argued that Darwin's theory couldn't explain how specific organismal forms developed and varied, explanations Mivart argued were necessary before Darwin could invoke the mechanism of natural selection to explain the evolution of species. To provide those explanations Mivart proposed theories of individuation and of instinct.

Boris Ephrussi studied fruit flies, yeast, and mouse genetics and development while working in France and the US during the twentieth century. In yeast, Ephrussi studied how mutations in the cytoplasm persisted across generations. In mice he studied the genetics of hybrids and the development of cancer. Working with George Wells Beadle on the causes of different eye colors in fruit flies, Ephrussi's research helped establish the one-gene-one-enzyme hypothesis. Ephrussi helped create new embryological techniques and contributed the theories of genetics and development.

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.