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

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Thomas Joseph King Jr. was a developmental biologist who, with fellow scientist Robert Briggs, pioneered a method of transplanting nuclei from blastula cells into fresh egg cells lacking nuclei. This method, dubbed nuclear transplantation, facilitated King's studies on cancer cell development. King's work was instrumental for the development of cloning of fish, insects, and mammals.

'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.

Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior (hereafter Infantile Autism) is a book written by Bernard Rimland, published in 1964. The book proposed a theory to explain the causes of autism. The book also synthesized research into autism and used Rimland's neural theory, described in the book, as a theory to explain some aspects of behavior, intelligence, and abnormality. Moreover, Infantile Autism contributed to a debate between Rimland and child psychologist Bruno Bettelheim in the 1960s over whether autism was caused by upbringing (see refrigerator mother theory) or by impaired brain development. Rimland's book convinced many autism researchers to look for abnormal psychological development.

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.

Leo Kanner published Autistic Disturbances of Affective Contact in 1943 in the journal Nervous Child. This article described the cases of eleven children with autism. Kanner described the behavior and upbringing of each child, aged two to eight, as well as the educational backgrounds of the children's. Though Eugen Bleuler, a professor of psychiatric at the University of Z rich and director of the Burgh lzli Asylum in Z rich in Z rich, Switzerland from 1898 to 1927, was first to use the term autism to describe of a symptom of schizophrenia, scientists cite Kanner's article as the first description of autism as a unique disease concept distinct from schizophrenia. One of the most cited articles about autism in the twentieth century, this article was the first to demarcate Kanner syndrome, which later called childhood autism. Researchers, including Kanner, eventually treated early infantile autism as a disorder resulting from abnormal development of the autistic children's brains.

In 1943, child psychiatrist Leo Kanner in the US gave the first account of Early Infantile Autism that encouraged psychiatrists to investigate what they called emotionally cold mothers, or refrigerator mothers. In 1949, Kanner published Problems of Nosology and Psychodynamics of Early Infantile Autism. In that article, Kanner described autistic children as reared in emotional refrigerators. US child psychiatrists claimed that some psychological or behavioral conditions might have origins in emotional or mental stress, meaning that they might be psychogenic. Kanner described autism's cause in terms of emotional refrigeration from parents into the early 1960s, often attributing autism to the lack of parental warmth. In the 1960s, Bernard Rimland in the US and Bruno Bettelheim in Austria disagreed on the role of psychogenesis in autism. Rimland suggested that autism's cause was rooted in neurological development, while Bettelheim continued to emphasize the role of nurturing during early childhood. Nevertheless, many mothers reported that they felt a deep sense of anguish and resentment toward child psychiatrists who often made them feel as if they were to blame for their children's autism.

Sir John Bertrand Gurdon further developed nuclear transplantation, the technique used to clone organisms and to create stem cells, while working in Britain in the second half of the twentieth century. Gurdon's research built on the work of Thomas King and Robert Briggs in the United States, who in 1952 published findings that indicated that scientists could take a nucleus from an early embryonic cell and successfully transfer it into an unfertilized and enucleated egg cell. Briggs and King also concluded that a nucleus taken from an adult cell and similarly inserted into an unfertilized enucleated egg cell could not produce normal development. In 1962, however, Gurdon published results that indicated otherwise. While Briggs and King worked with Rana pipiens frogs, Gurdon used the faster-growing species Xenopus laevis to show that nuclei from specialized cells still held the potential to be any cell despite its specialization. In 2012, the Nobel Prize Committee awarded Gurdon and Shinya Yamanaka its prize in physiology and medicine for for their work on cloning and pluripotent stem cells.

Leo Kanner studied and described early infantile autism in humans in the US during the twentieth century. Though Eugen Bleuler first coined the term autism in 1910 as a symptom of schizophrenia, Kanner helped define autism as a disease concept separate from schizophrenia. He helped found an early child psychiatry department in 1930 at the Johns Hopkins University Hospital in Baltimore, Maryland. Kanner revised criteria for diagnosing autism, beginning with his article Autistic Disturbances of Affective Contact in 1943, and he helped reclassify autism as a disorder caused by defective neurological development.