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

In February 1953, Linus Pauling and Robert Brainard Corey, two scientists working at the California Institute of Technology in Pasadena, California, proposed a structure for deoxyribonucleic acid, or DNA, in their article “A Proposed Structure for the Nucleic Acids,” henceforth “Nucleic Acids.” In the article, Pauling and Corey suggest a model for nucleic acids, including DNA, that consisted of three nucleic acid strands wound together in a triple helix. “Nucleic Acids” was published in Proceedings of the National Academy of Sciences shortly after scientists came to the consensus that genes, the biological factors that control how organisms develop, contained DNA. Though scientists proved Pauling and Corey’s model incorrect, “Nucleic Acids” helped scientists understand DNA’s structure and function as genetic material.

In April 1953, James Watson and Francis Crick published “Molecular Structure of Nucleic Acids: A Structure of Deoxyribose Nucleic Acid” or “A Structure for Deoxyribose Nucleic Acid,” in the journal Nature. In the article, Watson and Crick propose a novel structure for deoxyribonucleic acid or DNA. In 1944, Oswald T. Avery and his group at Rockefeller University in New York City, New York published experimental evidence that DNA contained genes, the biological factors called genes that dictate how organisms grow and develop. Scientists did not know how DNA’s function led to the passage of genetic information from cell to cell, or organism to organism. The model that Watson and Crick presented connected the concept of genes to heredity, growth, and development. As of 2018, most scientists accept Watson and Crick’s model of DNA presented in the article. For their work on DNA, Watson and Crick shared the 1962 Nobel Prize in Physiology or Medicine with Maurice Wilkins.

Max Ludwig Henning Delbrick applied his knowledge of theoretical physics to biological systems such as bacterial viruses called bacteriophages, or phages, and gene replication during the twentieth century in Germany and the US. Delbrück demonstrated that bacteria undergo random genetic mutations to resist phage infections. Those findings linked bacterial genetics to the genetics of higher organisms. In the mid-twentieth century, Delbrück helped start the Phage Group and Phage Course in the US, which further organized phage research. Delbrück also contributed to the DNA replication debate that culminated in the 1958 Meselson-Stahl experiment, which demonstrated how organisms replicate their genetic information. For his work with phages, Delbrück earned part of the 1969 Nobel Prize for Physiology or Medicine. Delbrück's work helped shape and establish new fields in molecular biology and genetics to investigate the laws of inheritance and development.

In 1954 Max Delbruck published On the Replication of Desoxyribonucleic Acid (DNA) to question the semi-conservative DNA replication mechanism proposed that James Watson and Francis Crick had proposed in 1953. In his article published in the Proceedings of the National Academy of Sciences, Delbrück offers an alternative DNA replication mechanism, later called dispersive replication. Unlike other articles before it, On the Replication presents ways to experimentally test different DNA replication theories. The article sparked a debate in the 1950s over how DNA replicated, which culminated in 1957 and 1958 with the Meselson-Stahl experiment supporting semi-conservative DNA replication as suggested by Watson and Crick. On the Replication played a major role in the study of DNA in the 1950s, a period of time during which scientists gained a better understanding of DNA as a whole and its role in genetic inheritance.

In 1956, Gunther Stent, a scientist at the University of California Berkeley in Berkeley, California, coined the terms conservative, semi-conservative, and dispersive to categorize the prevailing theories about how DNA replicated. Stent presented a paper with Max Delbrück titled “On the Mechanism of DNA Replication” at the McCollum-Pratt Symposium at Johns Hopkins University in Baltimore, Maryland. In response to James Watson and Francis Crick’s proposed structure of DNA in 1953, scientists debated how DNA replicated. Throughout the debate, scientists hypothesized different theories about how DNA replicated, but none of the theories had sound experimental data. Stent introduced DNA replication classes that, if present in DNA, would yield distinct experimental results. Conservative, semi-conservative, and dispersive DNA replication categories shaped scientists' research into how DNA replicated, which led to the conclusion that DNA replicated semi-conservatively.

William Thomas Astbury studied the structures of fibrous materials, including fabrics, proteins, and deoxyribonucleic acid, or DNA, in England during the twentieth century. Astbury employed X-ray crystallography, a technique in which scientists use X-rays to learn about the molecular structures of materials. Astbury worked at a time when scientists had not yet identified DNA’s structure or function in genes, the genetic components responsible for how organisms develop and reproduce. He was one of the first scientists to use X-ray crystallography to study the structure of DNA. According to historians, Astbury helped establish the field of molecular biology as he connected microscopic changes in the structure of materials to changes in their large-scale properties. Astbury and his images helped scientists to understand the structure of DNA and its role in genetics.

In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty published an article in which they concluded that genes, or molecules that dictate how organisms develop, are made of deoxyribonucleic acid, or DNA. The article is titled “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III,” hereafter “Transformation.” The authors isolated, purified, and characterized genes within bacteria and found evidence that those genes were made of DNA and not protein. Though scientists were initially skeptical that genes were made of DNA, they later recognized that the data reported in “Transformation” were clear evidence that DNA was genetic material, a revelation that furthered research about how organisms grow, develop, and pass on traits to offspring.

'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.

Between 1953 and 1957, before the Meselson-Stahl experiment verified semi-conservative replication of DNA, scientists debated how DNA replicated. In 1953, James Watson and Francis Crick proposed that DNA was composed of two helical strands that wound together in a coil. Their model suggested a replication mechanism, later termed semi-conservative replication, in which parental DNA strands separated and served as templates for the replication of new daughter strands. Many scientists, beginning with Max Delbrück, questioned Watson and Cricks’ model and suggested new theories for DNA replication. By 1957, three theories about DNA replication prevailed: semi-conservative, conservative, and dispersive replication. Then, Matthew Meselson and Franklin Stahl conducted the Meselson-Stahl experiment, which returned results that supported the semi-conservative theory of DNA replication. The collaboration among scientists that ultimately produced concrete evidence of the DNA replication mechanism furthered both theoretical and physical explanations of genetics and molecular biology, providing insight into how life develops, reproduces, and evolves.