Roger Wolcott Sperry studied the function of the nervous system in the US during the twentieth century. He studied split-brain patterns in cats and humans that result from separating the two hemispheres of the brain by cutting the corpus callosum, the bridge between the two hemispheres of the brain. He found that separating the corpus callosum the two hemispheres of the brain could not communicate and they performed functions as if the other hemisphere did not exist. Sperry studied optic nerve regeneration through which he developed the chemoaffinity hypothesis. The chemoaffinity hypothesis stated that axons, the long fiber-like process of neurons, connect to their target cells through special chemical markers. This challenged the previously accepted resonance principle of neuronal connection. Sperry shared the 1981 Nobel Prize in Physiology or Medicine with David Hubel and Torsten Wiesel.

The syncytial theory of neural development was proposed by Victor Hensen in 1864 to explain the growth and differentiation of the nervous system. This theory has since been discredited, although it held a significant following at the turn of the twentieth century. Neural development was well studied but poorly understood, so Hensen proposed a simple model of development. The syncytial theory predicted that the nervous system was composed of many neurons with shared cytoplasm. These nerves were thought to be present in the embryo from a very early stage and were selected by the function of the target tissue. There were two competing theories to the syncytial theory. Theodor Schwann and Francis Maitland Balfour proposed the sheath cell theory, which states that nerve fibers were the product of secretions by chains of sheath cells. Santiago Ramón y Cajal and Wilhelm His proposed the outgrowth theory of fiber development for individual neurons. The most substantial evidence against the syncytial theory of neural development was produced by Ross Granville Harrison in his studies of the development of nerve fibers.

Viktor Hamburger was an embryologist who focused on neural development. His scientific career stretched from the early 1920s as a student of Hans Spemann to the late 1980s at Washington University resolving the role of nerve growth factor in the life of neurons. Hamburger is noted for his systematic approach to science and a strict attention to detail. Throughout his life he maintained an interest in nature and the arts, believing both were important to his scientific work.

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.