Mesoderm is one of the three germ layers, groups of cells that interact early during the embryonic life of animals and from which organs and tissues form. As organs form, a process called organogenesis, mesoderm interacts with endoderm and ectoderm to give rise to the digestive tract, the heart and skeletal muscles, red blood cells, and the tubules of the kidneys, as well as a type of connective tissue called mesenchyme. All animals that have only one plane of symmetry through the body, called bilateral symmetry, form three germ layers. Animals that have only two germ layers develop open digestive cavities. In contrast, the evolutionary development of the mesoderm allowed in animals the formation of internal organs such as stomachs and intestines (viscera).

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.

In 2005, Ernest McCulloch and James Till published the article “Perspectives on the Properties of Stem Cells,” which discusses the various properties and future possibilities for the use of stem cells. Stem cells are unspecialized cells that can develop into several different cell types. In the article published in the journal Nature on 1 October 2005, the authors say they wrote the article to dispel misconceptions about what stem cells are, what they do, address some controversies surrounding stem cells, and discuss potential uses of stem cells. In the article, McCulloch and Till reveal how stem cell research has revolutionized cancer treatment as well as set the stage for future embryonic and adult stem cell research.

Between February 1969 and August 1970 Edward Kollar and Grace Baird, from the University of Chicago in Chicago, Illinois, published three papers that established the role of the mesenchyme in tooth induction. Drawing upon a history of using tissue interactions to understand differentiation, Kollar and Baird designed their experiments to understand how differentiated structures become specified. Their work overturned a widely accepted model that epithelium controls the identity of the structure, a phenomenon called structural specificity. Interactions between epithelium and mesenchyme control the development and differentiation of many parts during embryonic development, including structures like the gastrointestinal tract and hair. Thus, the realization that mesenchyme drives induction and differentiation during epithelio-mesenchymal interactions had far-reaching effects.

A germ layer is a group of cells in an embryo that interact with each other as the embryo develops and contribute to the formation of all organs and tissues. All animals, except perhaps sponges, form two or three germ layers. The germ layers develop early in embryonic life, through the process of gastrulation. During gastrulation, a hollow cluster of cells called a blastula reorganizes into two primary germ layers: an inner layer, called endoderm, and an outer layer, called ectoderm. Diploblastic organisms have only the two primary germ layers; these organisms characteristically have multiple symmetrical body axes (radial symmetry), as is true of jellyfish, sea anemones, and the rest of the phylum Cnidaria. All other animals are triploblastic, as endoderm and ectoderm interact to produce a third germ layer, called mesoderm. Together, the three germ layers will give rise to every organ in the body, from skin and hair to the digestive tract.

Elizabeth Dexter Hay studied the cellular processes that affect development of embryos in the US during the mid-twentieth and early twenty-first centuries. In 1974, Hay showed that the extracellular matrix, a collection of structural molecules that surround cells, influences cell behavior. Cell growth, cell migration, and gene expression are influenced by the interaction between cells and their extracellular matrix. Hay also discovered a phenomenon later called epithelial-mesenchymal transition, a process that occurs during normal embryo and adult development in which epithelial cells, cells that line external and internal surfaces of the body, transform into mesenchymal stem cells, connective tissue cells that are capable of turning into other cell types. Hay's work helped researchers explain normal developmental processes and enabled research into abnormal processes that can cause developmental defects and diseases.

In 1962 researcher John Bertrand Gurdon at the University of Oxford in Oxford, England, conducted a series of experiments on the developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. In the experiments, Gurdon conducted nuclear transplantation, or cloning, of differentiated cells, or cells that have already specialized to become one cell type or another, in tadpoles. Gurdon's experiment showed that differentiated adult cells could be induced to an undifferentiated state, where they could once again become multiple cell types. Gurdon's experiment disproved the theory that differentiated cells could not be undifferentiated or dedifferentiated into a new type of differentiated cell. Gurdon's experiment demonstrated nuclear transplantation, also called cloning, using differentiated cells.

As mice embryos develop, they undergo a stage of development called gastrulation. The hallmark of vertebrate gastrulation is the reorganization of the inner cell mass (ICM) into the three germ layers: ectoderm, mesoderm, and endoderm. Mammalian embryogenesis occurs within organisms; therefore, gastrulation was originally described in species with easily observable embryos. For example, the African clawed frog (Xenopus laevis) is the most widely used organism to study gastrulation because the large embryos develop inside a translucent membrane. Domestic chicken (Gallus gallus) gastrulation was also an early model organism because researchers could open the egg during development to look inside. Despite the challenges associated with studying mammalian gastrulation, the common house mouse (Mus musculus) has helped to shed light on the unique adaptations associated with mammalian development, and on the subtle differences in structure that give rise to significant divergence in late embryogenesis.

Mesenchyme is a type of animal tissue comprised of loose cells embedded in a mesh of proteins and fluid, called the extracellular matrix. The loose, fluid nature of mesenchyme allows its cells to migrate easily and play a crucial role in the origin and development of morphological structures during the embryonic and fetal stages of animal life. Mesenchyme directly gives rise to most of the body's connective tissues, from bones and cartilage to the lymphatic and circulatory systems. Furthermore, the interactions between mesenchyme and another tissue type, epithelium, help to form nearly every organ in the body.

Research in chemical induction seeks to identify the compound or compounds responsible for differentiation in a developing embryo. Soren Lovtrup compared the search for these compounds to the search for the philosopher's stone. It was based on the assumption that the differentiating agents have to be chemical substances either within cells or in the extracellular matrix. However, despite numerous efforts to understand them, the nature of these substances remained largely a mystery from the 1930s until the 1980s, when the new era of molecular induction based on molecular genetics provided a new perspective. During the period of emphasis on chemical induction, a variety of different experiments were conducted aimed at discovering the chemical nature of the inducer. In some experiments, the organizer region was killed by heat to assess the inducing ability of a dead organizer. Other experiments used natural and synthetic compounds to attempt. Although none of these experiments identified a chemical inducer with any certainty, they did discover many related properties of the developing embryo.