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

Fetal programming, or prenatal programming, is a concept that suggests certain events occurring during critical points of pregnancy may cause permanent effects on the fetus and the infant long after birth. The concept of fetal programming stemmed from the fetal origins hypothesis, also known as Barker’s hypothesis, that David Barker proposed in 1995 at the University of Southampton in Southampton, England. The fetal origins hypothesis states that undernutrition in the womb during middle to late pregnancy causes improper fetal growth, which in turn, causes a predisposition to certain diseases in adulthood. In addition to nutritional impacts, researchers have studied the fetal programming effects of many factors, such as maternal anxiety or violence during pregnancy. Researchers proposing the concept of fetal programming established a new area of research into the developmental causes of disease, pointing towards the in utero environment and its critical role in healthy human 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.

In 2011, Sarah McMahon and colleagues published “The Impact of Emotional and Physical Violence During Pregnancy on Maternal and Child Health at One Year Post-partum,” hereafter, “The Impact,” in the journal, Child and Youth Services Review. While existing studies had indicated negative chronic effects resulting from intimate partner violence, or IPV, such as miscarriage and premature labor, there was little research specifically analyzing the separate and joint effects of psychological and physical abuse on pregnant women and fetuses. The authors reported that both physical and emotional IPV had negative impacts on the woman and child at one-year after birth, including worse overall health and increased likelihood of depression. In “The Impact,” the researchers analyzed the effects of partner abuse during pregnancy, distinguishing between the effects of emotional abuse and physical abuse on health outcomes for a pregnant woman and her offspring.

In 2001, Kevin M. Godfrey and David J.P. Barker published the article “Fetal Programming and Adult Health” in Public Health Nutrition, where they identified the significance of maternal nutrition during pregnancy to healthy offspring development. The authors describe the effects of maternal nutrition on fetal programming of cardiovascular disease. Fetal programming is when a specific event during pregnancy has effects on the fetus long after birth. The authors argue that fetuses may adapt to varying shifts in their environment in utero, such as slowed fetal growth in response to malnutrition. While those adaptations can be helpful in utero, the authors assert they may persist into adolescence and adulthood, causing conditions such as high blood pressure or diabetes. Godfrey and Barker assert that fetal adaptations to maternal malnutrition may be implicated in the development of cardiovascular disease in adulthood, and called for future research investigating additional fetal programming variables.

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.

Otto Rank studied how birth impacts individuals’ psychology and creates anxiety throughout their lives in Europe and the US during the nineteenth century. In his book The Trauma of Birth, Rank stated that birth was extremely traumatic and that one spent his or her whole life trying to recover from the experience of being born and harshly separated from the peaceful womb. He argued that the trauma experienced at birth is the source of all human suffering and the key to understanding anxiety later in life. He stated that the experience of birth was one’s earliest experience of anxiety, which served as the blueprint for all other anxiety related experiences in life. Through his work, Rank prompted studies in developmental embryology analyzing early mother-child relationships and problems in early psychological development.

In 2011, fetal researcher Vivette Glover published “Annual Research Review: Prenatal Stress and the Origins of Psychopathology: An Evolutionary Perspective,” hereafter, “Prenatal Stress and the Origins of Psychopathology,” in the Journal of Child Psychology and Psychiatry. In that article, Glover explained how an evolutionary perspective may be useful in understanding the effects of fetal programming. Fetal programming is a hypothesis that attempts to explain how factors during pregnancy can affect fetuses after birth. Researchers associate exposure to prenatal stress, or stress experienced before birth, with an increased likelihood of some mental disorders. Glover states that such outcomes may be traced back to a fetus’s response to stress during pregnancy, and that those outcomes may have been beneficial in the past. By taking an evolutionary approach toward understanding mental disorders, Glover provided insights for studying the lasting effects of maternal stress during pregnancy on children’s mental health.

In 2009, A. John Henderson and colleagues published “Mothers’ Anxiety During Pregnancy Is Associated with Asthma in Their Children,” hereafter, “Mothers’ Anxiety,” in The Journal of Allergy and Clinical Immunology. Previous studies had shown that maternal stress during pregnancy affects children’s health during childhood. The researchers explored the association of asthma in children with maternal anxiety during pregnancy. The cause of asthma is often unknown. Thus, the researchers tested the possibility that maternal anxiety may increase disease risk in the children, particularly the development of asthma. The authors reported a positive association between maternal anxiety during pregnancy and asthma in offspring, indicating the possibility of a causal relationship. The authors’ findings demonstrated the health effects of maternal stress during pregnancy on children’s physiological and immune development.