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

Edward Donnall Thomas, an American physician and scientist, gained recognition in the scientific community for conducting the first bone marrow transplant, a pioneering form of hematopoietic stem cell transplantation (HSCT). Bone marrow transplants are considered to be the first successful example of tissue engineering, a field within regenerative medicine that uses hematopoietic stem cells (HSCs) as a vehicle for treatment. Prior to Thomas's groundbreaking work, most blood-borne diseases, including certain inherited and autoimmune diseases, were considered lethal.

'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.

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.

Tissue engineering is a field of regenerative medicine that integrates the knowledge of scientists, physicians, and engineers into the construction or reconstruction of human tissue. Practitioners of tissue engineering seek to repair, replace, maintain, and enhance the abilities of a specific tissue or organ by means of living cells. More often than not stem cells are the form of living cells used in this technology. Tissue engineering is one of the disciplines involved in translating knowledge of developmental biology into the clinical setting. One focus that this field has taken is the understanding of tissue and organ development during embryogenesis, as this knowledge will open avenues to new applications of this technology.

The purpose of regenerative medicine, especially tissue engineering, is to replace damaged tissue with new tissue that will allow the body to resume normal function. The uniqueness of tissue engineering is that it can restore normal structure in addition to repairing tissue function, and is often accomplished using stem cells. The first type of tissue engineering using stem cells was hematopoietic stem cell transplantation (HSCT), a surgical procedure in which hematopoietic stem cells (HSCs) are infused into a host to treat a variety of blood diseases, cancers, and immunodeficiencies. While there is a standard procedure for the infusion of these cells into a donor, variations in the sources of hematopoietic stem cells, and in the relationship between donor and recipient, do produce some variability in the procedure.

The discovery of hematopoietic stem cells (HSCs) provided a pioneering step in stem cell research. HSCs are a type of multipotent adult stem cell, characterized by their ability to self-renew and differentiate into erythrocyte (red blood cell) and leukocyte (white blood cell) cell lineages. In terms of function, these cells are responsible for the continual renewal of the erythrocytes, leukocytes, and platelets in the body through a process called hematopoiesis. They also play an important role in the formation of vital organs such as the liver and spleen during fetal development. The early biological knowledge obtained from the studies of HSCs established the base of knowledge for understanding other stem cell systems. In addition, these cells have a vital role in furthering stem cell research for clinical applications. Regenerative medicine is a field of medicine that has applied HSCs to the treatment of blood-borne diseases such as leukemia and lymphoma and of cancer patients undergoing chemotherapy.

Renowned physician and scientist William Harvey is best known for his accurate description of how blood circulates through the body. While his published work on the circulation of blood is considered the most important of his academic life, Harvey also made significant contributions to embryology with the publication of his book Exercitationes de Generatione Animalium in 1651. In this book he established several theories that would set the stage for modern embryology and addressed many embryological issues including conception, embryogenesis, and spontaneous generation.

Bicoid is the protein product of a maternal-effect gene unique to flies of the genus Drosophila . In 1988 Christiane Nüsslein-Volhard identified bicoid as the first known morphogen . A morphogen is a molecule that determines the fate and phenotype of a group of cells through a concentration gradient across that developing region. The bicoid gradient, which extends across the anterior-posterior axis of Drosophila embryos, organizes the head and thorax.