Santiago Felipe Ramon y Cajal investigated brains in the nineteenth and twentieth centuries in Spain. He identified and individuated many components of the brain, including the neuron and the axon. He used chick embryos instead of adult animals, then customary in brain research, to study the development and physiology of the cerebellum, spinal cord, and retina. Ramon y Cajal received the Nobel Prize in Physiology and Medicine in 1906, along with Camillo Golgi, for his work on the structure of the nervous system.

In the early 1960s, John W. Saunders Jr., Mary T. Gasseling, and Lilyan C. Saunders in the US investigated how cells die in the developing limbs of chick embryos. They studied when and where in developing limbs many cells die, and they studied the functions of cell death in wing development. At a time when only a few developmental biologists studied cell death, or apoptosis, Saunders and his colleagues showed that researchers could use embryological experiments to uncover the causal mechanisms of apotosis. The researchers published many of their results in the 1962 paper 'Cellular death in morphogenesis of the avian wing.'

In 1974, Elizabeth Dexter Hay and Stephen Meier in the US conducted an experiment that demonstrated that the extracellular matrix, the mesh-like network of proteins and carbohydrates found outside of cells in the body, interacted with cells and affected their behaviors. In the experiment, Hay and Meier removed the outermost layer of cells that line the front of the eye, called corneal epithelium, from developing chick embryos. Prior to their experiment, scientists observed that corneal epithelium produced collagen, the primary component of the extracellular matrix, which provides structural support to cells throughout the body. In their experiment, Hay and Meier confirmed that the lens capsule, a collagen-containing structure of the eye’s extracellular matrix, induced the corneal epithelium to produce collagen. That result demonstrated that extracellular matrix interactions affect tissue development in developing embryos.

"In vitro Experiments on the Effects of Mouse Sarcomas 180 and 37 on the Spinal and Sympathetic Ganglia of the Chick Embryo" were experiments conducted by Rita Levi-Montalcini in conjunction with Viktor Hamburger and Hertha Meyer and published in Cancer Research in 1954. In this series of experiments, conducted at the University of Brazil, Levi-Montalcini demonstrated increased nerve growth by introducing specific tumors (sarcomas) to chick ganglia. Ganglia are clusters of nerve cells, from which nerve fibers emerge. This work led to the discovery of nerve growth factor (NGF) and later the Nobel Prize in Physiology or Medicine in 1986.

In this paper Viktor Hamburger and Rita Levi-Montalcini collaborated to examine the effects of limb transplantation and explantation on neural development. In 1947 Hamburger invited Levi-Montalcini to his lab at Washington University in St. Louis to examine this question. Independently, each had previously arrived at opposing conclusions based on the same data. Hamburger concluded that limb transplantations caused the ganglia to develop more connections and grow larger while Levi-Montalcini concluded that the ganglia first produce a large amount of neurons, then degenerate the unsuccessful neurons. She concluded that larger ganglia must be due to the increase in successful connections. This joint paper, published in the Journal of Experimental Zoology in 1949, corroborated the findings reported by Levi-Montalcini and established that nerve degeneration is an integral part of development.

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.

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