Ectoderm

Ectoderm is one of three germ layers—groups of cells that coalesce early during the embryonic life of all animals except maybe sponges, and from which organs and tissues form. As an embryo develops, a single fertilized cell progresses through multiple rounds of cell division. Eventually, the clump of cells goes through a stage called gastrulation [2], during which the embryo reorganizes itself into the three germ layers [3]: endoderm [4], ectoderm [5], and mesoderm [6]. After gastrulation [2], the embryo goes through a process called neurulation [7], which starts the development of nervous system.

newts. The embryos in which she had transplanted the dorsal lip developed an extra body, head, or other nervous system structure. The resultant newts indicated that the transplanted tissue had induced gastrulation [2] and neurulation [7] of surrounding tissue just as it would have in its parent embryo. Mangold's experiments proved that the germ layers [3] lacked absolutely determined derivatives, a result that dismantled germ layer theory. Additionally, this experiment exemplified a shift in embryological methods that had occurred in the late nineteenth century. Whereas most practitioners had focused on described and compared the anatomy of different embryos, some scientists began to physically manipulate embryos to test hypotheses. These methods helped spur the growth of programs that focused on experimental embryology [29] during the early twentieth century.
Following the work of Mangold and Spemann, other scientists experimented on the three germ layers [3] . Among these experimental embryologists was Sven Hörstadius at Uppsala University, in Uppsala, Sweden. Conducting experiments on echinoderms [30] , a phylum that includes sand dollars and sea urchins, Hörstadius investigated the ability of the germ layers [3] to transform. Among Hörstadius' major contributions was his work on the neural crest [10] , which culminated in a book in 1950 titled The Neural Crest: Its properties and derivatives in the light of experimental research.
Wilhelm His [26] at the University of Basel [31] , in Basel, Switzerland, had discovered neural crest [10] , a derivative of the neuroectoderm, in the chick [14] in 1868. His noticed that as the neural tube [8] closed, cells began to migrate away from midline; these cells eventually became called the neural crest [10] . Twenty years later scientists had begun to look for the derivatives of the neural crest [10] , especially in the head and nervous system. In 1893 Julia Platt, a doctoral student studying at Munich University, in Munich, Germany, published the results of her research on the ectodermal, specifically neural crest [10] , derivatives in the head. Based on her studies of Necturus maculosus [32] embryos, a type of aquatic salamander [33] , Platt showed that the cartilage of the branchial arches and parts of the teeth developed from ectoderm [5] .
Few scientists acknowledged the role of neural crest [10] in the formation of the skeleton until the 1940s when Hörstadius and Sven Sellman, in Sweden, and Gavin de Beer, in England, confirmed the role of neural crest [10] in skeletal development. During the 1960s, researchers studied how neural crest cells [34] migrate. Researchers like James Weston at Yale University [35] , in New Haven, Connecticut, and Malcolm Johnston, at the University of Rochester, in Rochester, New York, traced the migration of trunk and cranial neural crest [10] in chick [14] embryos. In the 1970s, Nicole Le Douarin, a researcher at the University of Nantes, in Nantes, France, created chimeric quail and chick [14] embryos to track the migration and derivatives of the neural crest [10] .
As some researchers investigated the derivatives and movements of neural crest [10] , others examined the interactions of the different germ layers [3] within the embryo. In 1969 Pieter D. Nieuwkoop, at the Royal Netherlands Academy of Arts and Science, in Utrecht, Holland, published an article that addressed the potential of endoderm [4] and ectoderm [5] to induce the formation of their surrounding tissues. Using embryos of the salamander [33] Ambystoma mexicanum [36] , Nieuwkoop showed that when endoderm [4] and ectoderm [5] interact, the endoderm [4] induces mesoderm [6] to form within the adjacent regions of ectoderm [5] . His experiments also demonstrated that the establishment of the ventral and dorsal regions of the embryo, known as the polarity [37] of the embryo, results from the interactions of the endoderm [4] and ectoderm [5] .
Scientists began to research the genetic signals responsible for gastrulation [2] in the mid-1980s. Families of signaling factors, such as Vg1/Nodal, Wnt, and FGF, produce proteins that help to pattern the embryo and to form the three germ layers [3] . In the 1990s, scientists began to show how the signals involved in gastrulation [2] also function in neurulation [7] . In particular, researchers studied the Bone Morphogenetic Protein, or BMP, pathway. This pathway of signals helps cause tissues to differentiate during gastrulation [2] , with inhibition of BMP causing the ectoderm [5] to differentiate into neuroectoderm, the tissue that gives rise to the nervous system. Researchers found that proteins like Chordin, Noggin, Follistatin, and Cerberus block the expression of different members of the BMP family. These BMP-inhibitors help to induce the ectoderm [5] to differentiate into the central and peripheral nervous systems.