Embryo Project Encyclopedia Articles

Conrad Hal Waddington's "Experiments on Embryonic Induction III," published in 1934 in the Journal of Experimental Biology, describes the discovery that the primitive streak induces the mammalian embryo. Waddington's hypothesis was that a transplanted primitive streak could induce neural tissue in the ectoderm of the rabbit embryo. The primitive streak defines the axis of an embryo and is capable of inducing the differentiation of various tissues in a developing embryo during gastrulation. In this experiment Waddington was, in fact, able to induce neural differentiation. Waddington noted that the tissue is "competent"; for a chick organizer, and by deduction a mammalian organizer must exist. Competence refers to a cell's ability to respond to an inducing signal, which is temporally limited to certain developmental stages. Waddington's initial work laid the foundation for many decades of research to follow, including further experiments by Waddington with the mammalian organizer.

Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.

Samuel Randall Detwiler was an embryologist who studied neural development in embryos and vertebrate retinas. He discovered evidence for the relationship between somites and spinal ganglia, that transplanted limbs can be controlled by foreign ganglia, and the plasticity of ganglia in response to limb transplantations. He also extensively studied vertebrate retinas during and after embryonic development. Detwiler's work established many principles studied in later limb transplantation experiments and was identified by Viktor Hamburger as an important bridge between his and Ross Granville Harrison's research.

Edward B. Lewis studied embryonic development in Drosophila, including the discovery of the cis-trans test for recessive genes, and the identification of the bithorax complex and its role in development in Drosophila. He shared the 1995 Nobel Prize in Physiology or Medicine with Christiane Nüsslein-Volhard and Eric F. Wieschaus for work on genetic control of early embryonic development.

Stanley Cohen is a biochemist who participated in the discovery of nerve growth factor (NGF) and epidermal growth factor (EGF). He shared the 1986 Nobel Prize in Physiology or Medicine with Rita Levi-Montalcini for their work on the discovery of growth factors. His work led to the discovery of many other growth factors and their roles in development.

Conrad Hal Waddington was an embryologist and theoretical biologist. His early experimental work investigated aspects of embryonic induction and the properties of the organizer first identified by Hans Spemann and Hilde Mangold, while his later studies focused on genetic assimilation. Waddington is probably best known for developing the concept of the epigenetic landscape, and he also held significant interest in many different areas ranging from the visual arts and poetry to philosophy. Throughout his career, Waddington maintained that the arts were integral to science, and he continued to draw inspiration from the arts for his own work.

The Spemann-Mangold organizer, also known as the Spemann organizer, is a cluster of cells in the developing embryo of an amphibian that induces development of the central nervous system. Hilde Mangold was a PhD candidate who conducted the organizer experiment in 1921 under the direction of her graduate advisor, Hans Spemann, at the University of Freiburg in Freiburg, German. The discovery of the Spemann-Mangold organizer introduced the concept of induction in embryonic development. Now integral to the field of developmental biology, induction is the process by which the identity of certain cells influences the developmental fate of surrounding cells. Spemann received the Nobel Prize in Medicine in 1935 for his work in describing the process of induction in amphibians. The Spemann-Mangold organizer drew the attention of embryologists, and it spurred numerous experiments on the nature of induction in many types of developing embryos.

Conrad Hal Waddington's Organisers and Genes, published in 1940, is a summary of available research and theoretical framework for many concepts related to tissue differentiation in the developing embryo. The book is composed of two main conceptual sections. The first section explores the action and nature of the organizer, while the second section delves into genes and their influence on development.

In his 1907 paper, "Experiments in Transplanting Limbs and Their Bearing Upon the Problems of the Development of Nerves," in the Journal of Experimental Zoology that he edited, Ross Granville Harrison tested the development of nerves in transplanted tissue. He studied neural development by examining two competing theories. Victor Hensen proposed a syncytial theory as a way to explain neural development, suggesting that all the nerves of an embryo were connected directly by cytoplasm laid down early in development, and leaving no room for later modification. Santiago Ramón y Cajal proposed a competing outgrowth theory that nerves develop from the central nervous system, pushing through tissues by growing nerve fibers and growth cones. Harrison's experiment refuted many of the claims of the syncytial theory although it did not produce evidence that could directly prove the outgrowth theory.

"A Diffusible Agent of Mouse Sarcoma, Producing Hyperplasia of Sympathetic Ganglia and Hyperneurotization of Viscera in the Chick Embryo," by Rita Levi-Montalcini and Viktor Hamburger, appeared in 1953 in the Journal of Experimental Zoology. The paper provided the first evidence that nerve growth factor is a diffusible substance. Nerve growth promoting tumors were implanted into developing embryos to determine whether the tumors stimulated growth by direct contact or by a diffusible substance. The tumors were implanted into different parts of the embryo; one set of experiments implanted the tumor directly in the embryo, while another set of experiments placed the tumor on an exterior membrane. The membrane provided a barrier to direct contact with the nervous system, and allowed some chemical interaction between the tumor and the embryo. The tumor stimulated growth in both orientations, demonstrating that nerve growth factor was a chemical agent. The paper ends with two possible conclusions for the mechanism of nerve growth, the tumor may have been directly stimulating the ganglia by a diffusible signal, or it may have reduced the resistance of the chick tissues to the nerve growth. The term "nerve growth factor" is not explicitly used in this paper, and is referred to as a "diffusible agent" or a "growth promoting agent."