Embryo Project Encyclopedia

"Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics" (hereafter abbreviated as "Apoptosis") was published in the British Journal of Cancer in 1972 and co-authored by three pathologists who collaborated at the University of Aberdeen, Scotland. In this paper the authors propose the term apoptosis for regulated cell death that proceeds through active, controlled morphological changes. This is in contrast to necrosis, a passive mode of cell death that results from uncontrolled cellular reactions to injury or stress. The journal article also suggests that apoptosis plays crucial roles in various pathological and physiological conditions including the shaping of digits and the shrinking of vestigial organs in developing embryos.

Teratomas are embryonal tumors that normally arise from germ cells and are typically benign. They are defined as being composed either of tissues that are foreign to the area in which they form, or of tissues that derive from all three of the germ layers. Malignant teratomas are known as teratocarcinomas; these cancerous growths have played a pivotal role in the discovery of stem cells. "Teratoma" is Greek for "monstrous tumor"; these tumors were so named because they sometimes contain hair, teeth, bone, neurons, and even eyes. Teratomas have been medical curiosities for centuries, though it wasn't until the 1960s that significant research into mice teratomas elucidated not only what these strange growths were, but also how germinal cells should normally function.

Leo Loeb developed an experimental approach to studying cancer and pioneered techniques for tissue culture and in vitro tissue transplantation which impacted early-to-mid twentieth century experimental embryology. Loeb received his medical degree from the University of Zurich in 1897. As part of his doctorate, he completed a thesis on the outcomes of tissue transplantation in guinea pigs. Loeb's thesis inspired a life-long interest in tissue transplantation. His research culminated in greater than 400 publications, including a book called The Biological Basis of Individuality, in which he demonstrated the potential immortality of certain mammalian tissues.

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.

The review article “Cell Deaths in Normal Vertebrate Ontogeny” (abbreviated as “Cell Deaths”) was published in Biological Reviews of the Cambridge Philosophy Society in 1951. The author, Alfred Glücksmann, was a German developmental biologist then working at the Strangeways Research Laboratory, Cambridge, England. In “Cell Deaths,” Glücksmann summarizes observations about cell death in normal vertebrate development that he had compiled from literature published during the first half of the twentieth century. “Cell Deaths” emphasizes the frequent occurrence of cell death in various locations and stages of development, and suggests that cell death functions as a crucial mechanism in integrating cells into tissues and organs in normal vertebrate ontogeny.

Edward Charles Dodds researched the function and effects of natural and artificial hormones on the endocrine system in England during the twentieth century. Though he first worked with hormones such as insulin, Dodds focused on the effects of estrogen in the body and how to replicate those effects with artificial substances. In 1938, along with chemist Robert Robinson, Dodds synthesized the first synthetic estrogen called diethylstilbestrol. Despite the wide use of diethylstilbestrol to treat a variety of hormonal problems like miscarriages during pregnancy and menopause, Dodds argued against the use of synthetic substances in the human body due to their unknown effects. Just before Dodds's death, his hypotheses were confirmed when researchers showed that people exposed to diethylstilbestrol often developed cancer. Dodds was one of the first researchers to investigate the endocrine or hormone system in humans, and his research led to the creation of other synthetic hormones used in contraceptive pills and hormone replacements.

Percivall Pott was a physician in England during the eighteenth century who identified soot as the cause of chimney sweeps' scrotal cancer, later called testicular cancer. In the 1770s, Pott observed that scrotal cancer commonly afflicted chimney sweeps, the young boys sent up into chimneys to clean away the soot left over from fires, and he hypothesized that the soot inside chimneys might cause that type of cancer. Pott was one of the first doctors to identify some environmental factor as causing cancer. Pott's research helped chimney sweeps to prevent scrotal cancer by using protective clothing, and it also allowed for future research on environmental causes of cancers.

The spinal column is the central structure in the vertebrate body from which stability, movement, and posture all derive. The vertebrae of the spine are organized into four regions (listed in order from cranial to caudal): cervical, thoracic, lumbar, and pelvic. These regions are classified by their differences in curvature. The human spine usually consists of thirty-three vertebrae, seven of which are cervical (C1-C7), twelve are thoracic (T1-T12), five are lumbar (L1-L5), and nine are pelvic (five fused as the sacrum and four fused as the coccyx).

Beatrice Mintz is a brilliant researcher who has developed techniques essential for many aspects of research on mouse development. She produced the first successful mouse chimeras and meticulously characterized their traits. She has worked with various cancers and produced viable mice from the cells of a teratoma. Mintz participated in the development of transgenic mice by the incorporation of foreign DNA into a mouse genome. Her techniques have been widely applied to other studies of mouse development and are so common that many of the publications that utilize her techniques no longer remember to cite the source.

This diagram shows how NCCs migrate differently in rats, birds and amphibians. The arrows represent both chronology of NCCs migration and the differential paths that NCCs follow in different classes of animals. The solid black portion of each illustration represents the neural crest, and the large black dots in (c) and in (f) represent the neural crest cells. The speckled sections that at first form a basin in (a) and then close to form a tube in (f) represent the neural ectoderm. The solid white portions represent the epidermal ectoderm. During the neurula stage of all vertebrate embryos (a), the neural crest is located in two places on the neural plate. As the neural tube forms (b), a process called neurulation, the neural crest moves with the folding plate as it forms the junction between the neural and epidermal ectoderm. NCCs migrate differently in different classes of vertebrates (c-f). For instance, in rats (c), the NCCs migrate away from the neural crest before neurulation completes and while the neural fold is still open. In birds (d and f), neural crest cells do not migrate until the neural fold closes. In amphibians (e and f), the neural crest cells migrate after neurulation completes, and only after the cells have accumulated above the neural tube. Subsequently, NCCs will all migrate down their specialized pathways and diversify into the several sub-types of NCCs.