Conrad Hal Waddington's "Experiments on the Development of Chick and Duck Embryos, Cultivated in vitro," published in 1932 in Philosophical Transactions of the Royal Society of London, Series B, compares the differences in the development of birds and amphibians. Previous experiments focused on the self differentiation of individual tissues in birds, but Waddington wanted to study induction in greater detail. The limit to these studies had been the amount of time an embryo could be successfully cultivated ex vivo. Waddington applied in vitro cell culturing techniques to this experiment, as opposed to the chorio-allantoic technique used in many earlier studies. Culturing in vitro consisted of placing the embryo on a clot of adult chicken blood plasma and chick embryo extract in a watch glass. Experiments reported in this paper were divided into three main sections: the development of the embryos in vitro, induction by the endoderm, and induction by the primitive streak.
German embryologist Viktor Hamburger came to the US in 1932 with a fellowship provided by the Rockefeller Foundation. Hamburger started his research in Frank Rattray Lillie's laboratory at the University of Chicago. His two-year work on the development of the central nervous system (CNS) in chick embryos was crystallized in his 1934 paper, "The Effects of Wing Bud Extirpation on the Development of the Central Nervous System in Chick Embryos," published in The Journal of Experimental Zoology. Hamburger was able to use the microsurgical techniques that he had learned from Hans Spemann to show how wing buds influence the development of the CNS in chick embryos. This paper is one of several among Hamburger's important studies on chick embryos and represents the empirical and theoretical cornerstone for his further research on central-peripheral relations in the development of the nervous system.
An important question throughout the history of embryology is whether the formation of a biological structure is predetermined or shaped by its environment. If both intrinsic and environmental controls occur, how exactly do the two processes coordinate in crafting specific forms and functions? When Viktor Hamburger started his PhD study in embryology in the 1920s, few neuroembryologists were investigating how the central neurons innervate peripheral organs. As Hamburger began his research, he had no clue that central-peripheral relations in the development of the central nervous system (CNS) would become one of his major interests for the next seventy-five years. In fact, this research trajectory would lead him to discover programmed cell death as a pivotal mechanism mediating central-peripheral relations, as well as to Nobel-Prize-winning work on nerve growth factors (NGF).
The p53 protein acts as a pivotal suppressor of inappropriate cell proliferation. By initiating suppressive effects through induction of apoptosis, cell senescence, or transient cell-cycle arrest, p53 plays an important role in cancer suppression, developmental regulation, and aging. Its discovery in 1979 was a product of research into viral etiology and the immunology of cancer. The p53 protein was first identified in a study of the role of viruses in cancer through its ability to form a complex with viral tumor antigens. In the same year, an immunological study of cancer also found p53 due to its immunoreactivity with tumor antisera. Although a series of studies found p53 through various routes, and various researchers called it different names, it was eventually confirmed that they had all encountered the same protein, p53.
Through various studies developmental biologists have been able to determine that the muscles of the back, ribs, and limbs derive from somites. Somites are blocks of cells that contain distinct sections that diverge into specific types (axial or limb) of musculature and are an essential part of early vertebrate development. For many years the musculature of vertebrates was known to derive from the somites, but the exact developmental lineage of axial and limb muscle progenitor cells remained a mystery until Nicole Le Douarin and Charles P. Ordahl published "Two Myogenic Lineagues within the Developing Somite" in 1991. This paper describes their experiment, which used chick-quail chimeras to demonstrate the exact lineage of the limb and back musculature.
Richard A. Lockshin's 1963 PhD dissertation on cell death in insect metamorphosis was conducted under the supervision of Harvard insect physiologist Carroll M. Williams. Lockshin and Williams used this doctoral research as the basis for five articles, with the main title "Programmed Cell Death," that were published between 1964 and 1965 in the Journal of Insect Physiology. These articles examine the cytological processes, neuronal and endocrinal controls, and the influence of drugs on the mechanism of cell death observed in pupal muscle structures of the American silkmoth. Those muscle structures disappeared right after the completion of adult development. Several scientists have credited this series of articles as introducing the now standard term "programmed cell death." Among the five articles, "Endocrine Potentiation of the Breakdown of the Intersegmental Muscles of Silkmoths" (abbreviated hereafter as "Endocrine Potentiation") was published first and has been cited the most often. The article suggests that the endocrinal conditions at the beginning of the adult development are necessary, but not sufficient, for precisely scheduling three weeks later the cell death activities in the pupal intersegmental muscles of American silkmoths. The research was among the first to attempt to pinpoint the role of hormones in regulating cell death, a process integral to development.
Hans Adolf Eduard Driesch was a late-nineteenth and early-twentieth century philosopher and developmental biologist. In the spring of 1891 Driesch performed experiments using two-celled sea urchin embryos, the results of which challenged the then-accepted understanding of embryo development. Driesch showed that the cells of an early embryo, when separated, could each continue to develop into normal larval forms. This finding contrasted with Wilhelm Roux's experiments with frog eggs from which Roux concluded that embryonic cells have predetermined fates - they cannot form into one thing when separated, and a different form when left unseparated. To Roux, embryos were made up of a mosaic of cells, all of which were important and necessary for the viable embryos to form. Driesch, on the other hand, was able to show that individual cells resulting from cleavage of the fertilized egg were all able to form into viable embryos, and not just predetermined parts that Roux believed.
Ann Campbell Burke examines the development and evolution of vertebrates, in particular, turtles. Her Harvard University experiments, described in Development of the Turtle Carapace: Implications for the Evolution of a Novel Bauplan, were published in 1989. Burke used molecular techniques to investigate the developmental mechanisms responsible for the formation of the turtle shell. Burke's work with turtle embryos has provided empirical evidence for the hypothesis that the evolutionary origins of turtle morphology depend on changes in the embryonic and developmental mechanisms underpinning shell production.
In November 2007, Masato Nakagawa, along with a number of other researchers including Kazutoshi Takahashi, Keisuke Okita, and Shinya Yamanaka, published "Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts" (abbreviated "Generation") in Nature. In "Generation," the authors point to dedifferentiation of somatic cells as an avenue for generating pluripotent stem cells useful for treating specific patients and diseases. They provide background to their research by observing that previous attempts to reprogram somatic cells to a state of greater differentiability with retroviral factors Oct3/4, Sox2, c-Myc, and Klf4 had succeeded in producing induced pluripotent stem (iPS) cells that contributed to viable adult chimeras and possessed germline competency. However, as they note, the c-Myc retrovirus contributes to tumors in generated chimeras, rendering iPS cells produced with c-Myc useless for clinical applications. The authors attempt to overcome this problem by modifying the standard protocol for producing iPS cells in mice in such a way that the c-Myc retrovirus is removed. They identify problems and benefits associated with this method, but most importantly note that their method generated iPS cells that did not cause tumors in chimeric mice. Nakagawa and colleagues also report that they successfully reprogrammed adult dermal fibroblasts to return to a pluripotent state without c-Myc.
Jacques Loeb developed procedures to make embryos from unfertilized sea urchin eggs in 1899. Loeb called the procedures "artificial parthenogenesis," and he introduced them and his results in "On the Nature of the Process of Fertilization and the Artificial Production of Norma Larvae (Plutei) from the Unfertilized Eggs of the Sea Urchin" in an 1899 issue of The American Journal of Physiology. In 1900 Loeb elaborated on his experiments. Following those publications, however, he discovered he had used inaccurately labeled salts and redid his experiments to determine the correct amount of salts needed for artificial parthenogenesis.