It is the innermost of the three germ layers, or cell masses (found in the ectoderm and mesoderm), that appear early in the development of an animal embryo.
The endoderm subsequently gives rise to the epithelium of the pharynx, including the Eustachian tube, tonsils, thyroid gland, parathyroid glands, and thymus gland; the larynx , trachea, and lungs; the gastrointestinal tract (except the mouth and anus), the urinary bladder, the vagina (in women), and the urethra.
The term endoderm is sometimes used to refer to the gastrodermis , the simple tissue that lines the digestive cavity of cnidarians and ctenophores.
Germ layers are formed during gastrulation, although cells are specified even earlier in development. The cells that will become the endoderm are found in the plant half of the egg, adjacent to the equatorial band.
It has been suggested that the future fate of the endoderm cell is predetermined by maternal factors in the egg.
It has been observed in mice that cells from the primitive endoderm on the surface of the blastula that are adjacent to the blastocele, the fluid-filled cavity in the early blastocyst, will develop into extra-embryonic membranes.
These include both the parietal endoderm, which will form Reichert’s membrane, and the visceral endoderm, a protective membrane that surrounds the cylinder of the egg.
Although the endoderm will eventually develop into internal structures, future endodermal cells are initially found on the surface of the blastula.
During the gastrulation process, the cells of the developing embryo are drastically rearranged so that the germ layers end in the correct positions.
The endoderm migrates into the embryo as a sheet of cells in amphibians (known as involution) or as individual cells in birds and mammals (Ingression).
Cellular aspects of the appearance of the endoderm
Appearance of the definitive endoderm in gastrulation
The definitive endoderm in Amniotes arises at the time of gastrulation, during which the endoderm precursors are initially located at the entrance of the epiblast in the anterior primitive streak.
Definitive endoderm cells emerge from the primitive streak and insert into the visceral endoderm. Visceral forms are found in most extra-embryonic tissues, but they also contribute some cells to the gastrointestinal tract.
Recent observations suggest that cells originating from the visceral endoderm of the epiblast intermingle between the visceral cells rather than shifting it like a lamina to the anterior and lateral regions of the concept.
The directionality of movement is controlled by the mesoderm derivative Sdf1 / Cxcl12b that acts on the endoderm that expresses Cxcr4 in zebrafish and Xenopus.
Genetic modifications of the mosaic in zebrafish have shown that, at least in this model, endoderm gastrulation is a combination of active cell movements and passive movements by which a cell is mobilized by its neighbors.
Animal polar cell subpopulations forced to express Sox17, an inducer of endoderm, migrate to the endodermal layer or die. These observations suggest that there is a feedback check on the match between a cell’s state of differentiation and its environment.
The latter considerations, in the context of embryonic stem cell cultures, may allow endodermal cells to aggregate in a heterogeneous culture or die depending on their neighbors.
Timing of the endoderm specification
In mice and chicks, heterotopic grafting experiments have shown that the determination to form the endoderm occurs after the cells have left the streak.
Whether the epithelial-mesenchymal transition is crucial for endoderm differentiation is unclear at this time, but the endoderm’s ability to differentiate prior to gastrulation in various species argues against this hypothesis.
However, in Amniotes, the cells are exposed to the signaling centers during their migration.
In chicken, the endoderm progenitors in Koller’s sickle undergoing their characteristic ‘Polonaise movement’ are believed to be specified by receiving signals from the posterior marginal zone that activate the Nodal signaling pathway.
These signals include Wnt ligands. At a later stage, the mesoderm and endoderm in passing can receive instructive pattern signals from the node.
Such signaling centers are formed in embryonic stem cell cultures aggregated in embryoid bodies and most likely in dense monolayer cultures.
By sensing their position relative to the signaling center, moving cells could coordinate their differentiation.
With the notable exception of the sea urchin, most species initially secrete ectoderm precursors from parents that give rise to endoderm and mesoderm.
In Caenorhabditis elegans, the sea urchin and zebrafish mesoderm and endoderm are derived from bipotential progenitors.
A similar mesendoderm population has been postulated in Amniotes based on the co-expression of endoderm and mesoderm markers in the anterior streak, and the observation that certain signaling cascades induce both cell types.
In space, endodermal / mesendodermal progenitors tend to be located in the anterior line while mesodermal parents extend to the posterior line.
However, single cell lineage tracing has never formally demonstrated the existence of bipotential cells in Aminotes.
The endoderm will become the digestive tract (or intestine), as well as a number of associated organs and glands. It will give rise to the lungs, liver, and pancreas, as well as the thymus, thyroid, and parathyroid glands.
Additionally, endoderm cells will form the lining of many of the body’s organ systems, including the respiratory system, digestive system, urinary system, and reproductive system.
The intestine is formed during gastrulation when the endoderm and mesoderm move within the embryo in a process called intussusception.
As cells move into the embryo, the dorsal endoderm forms a cell line along the mesoderm and a gap forms between the dorsal endoderm and plant endoderm cells.
This gap is the archenteron which is the precursor to the intestinal cavity.
The endoderm, along with the other two germ layers, was discovered in 1817 by Christian Pander , a doctoral student at the University of Würzburg, in Würzburg, Germany.
In his dissertation, Beiträge zur Entwickelungsgeschichte des Hühnchens im Eie (contributions to the evolutionary history of the chicken in the egg), Pander described how two layers give rise to one third in the chicken embryo (Gallus gallus).
Pander’s description of the formation of these layers is the first description of gastrulation in chicken, and it informed future studies of the layers of germs.
Martin Rathke at the University of Königsberg, in Königsberg, Prussia (later in Poland), soon found evidence in a developing crab, Astacus astacus, of the two layers that Pander had described.
Rathke’s discovery marked the first discovery of endoderm and ectoderm in an invertebrate, but that information was not investigated for more than two decades.
Germ layers came to the attention of many scientists in the nineteenth century. Karl Ernst von Baer of the University of Königsberg expanded the concept of germ layers to include all vertebrates in his 1828 text “On the Evolutionary History of Animals. Observations and reflections ”.
Twenty years later, the natural historian Thomas Henry Huxley , in England, applied Pander’s concept of germ layers to jellyfish.
In his 1849 paper “On the Anatomy and Affinities of the Jellyfish Family,” Huxley observed that the two layers of cells he saw in adult jellyfish were related to each other in the same way as germ layers in embryos of chicken described by Pander .
Huxley’s association between the body plan of the adult jellyfish and the vertebrate embryo connected the study of growth and development, called ontogeny, with the study of relationships between organisms, called phylogeny.
Huxley’s support for a relationship between ontogeny and phylogeny, later known as the recapitulation theory, would be central to the works of late 19th century scientists such as Charles Darwin of England and Ernst Haeckel of the University of Jena, in Germany.
These and other scientists began looking for embryos to evidence evolution.
In the 1860s, researchers compared the layers of germs throughout the animal kingdom. Beginning in 1864, the embryologist Aleksandr Kovalevsky , who studied embryology at the University of Saint Petersburg in Russia, studied invertebrates.
Their research showed that invertebrate embryos had the same primary germ layers, endoderm and ectoderm, as vertebrate embryos, and that the layers arose in the same way throughout the animal kingdom.
Kovalevsky’s findings convinced many of the universality of germ layers, a result that some scientists formulated as a principle of germ layer theory.
The germ layer theory held that each of the germ layers, regardless of species, gave rise to a fixed set of organs. These organs were considered homologous throughout the animal kingdom, effectively linking ontogeny with phylogeny.
Scientists like Haeckel in Germany and Edwin Ray Lankester at University College London in England convinced many to accept the germ layer theory in the late 19th century.
While the germ layer theory gained wide support, it was not accepted by all. Beginning in the late 19th century, embryologists such as Edmund Beecher Wilson , in the United States, and Wilhelm His and Rudolf Albert von Kölliker , both in Germany, opposed the absolute universality of germ layers that the theory demanded.
These opponents of the germ layer theory mainly belonged to a new tradition of embryologist (those who used physical manipulations of embryos for the development of research).
In the 1920s, experiments by scientists such as Hans Spemann and Hilde Mangold in Germany and Sven Hörstadius in Sweden led scientists to dismantle the germ layer theory.
Scientists in the early 20th century tried to explain germ layers more fully by investigating how embryos transformed from one cell to thousands of cells.
Among these embryologists, Edwin Grant Conklin at the University of Pennsylvania in Philadelphia, Pennsylvania, was one of the first to trace cell lines from the single cell stage.
In his 1905 text The Organization and Lineage of the Ascidian Egg Cell, Conklin traced the divisions and subsequent specialization of cells in the embryo of a sea squirt, a type of marine invertebrate that develops a tough outer shell and adheres to the bottom of the sea by creating a plot, or destination map, of the development path of each of the cells.
Conklin located the precursor cells, traced the formation of each of the germ layers, and showed that even in very early stages of development, cells to differentiate become restricted.
Conklin’s fate mapping experiments , along with questions about the differentiating ability of cells, influenced scientists such as Robert Briggs of Indiana University in Bloomington, Indiana, and his collaborator, Thomas King , at the Research Institute. Cancer in Philadelphia, Pennsylvania.
In the 1950s, Briggs and King began a series of experiments to assess the developmental capacity of cells and embryos. In 1957, Briggs and King transplanted nuclei of the presumed endoderm of the northern leopard frog, Rana pipiens, into eggs from which they had removed the nuclei.
This technique, which Briggs and King helped create, called nuclear transplantation, allowed them to explore the timing of cell differentiation and the technique became the basis for future cloning experiments.
From their nuclear transplantation experiments, Briggs and King discovered that during endodermal differentiation, the ability of the nucleus to help cells specialize is progressively restricted.
That result was supported in 1960 by the work of John Gurdon , at the University of Oxford in Oxford, England. Gurdon recreated Briggs and King’s experiments using the African clawed frog, Xenopus laevis, and Gurdon found that there are significant differences between species in the speed and timing of these endodermal restrictions.
While Briggs , King and Gurdon worked to understand the restriction of cellular endodermal fates, other scientists, such as Pieter Nieuwkoop , at the Royal Dutch Academy of Arts and Sciences, in Utrecht, the Netherlands, investigated the formation of germ layers.
In 1969, Nieuwkoop published an article entitled “The formation of the mesoderm in urodelean amphibians I. Induction by the endoderm”, in which he examined the interactions of the endoderm and the ectoderm.
Nieuwkoop divided the embryos of the salamander, Ambystoma mexicanum, into regions of presumed endoderm and presumed ectoderm. When it was allowed to develop in isolation, the mesoderm did not form.
But when it recombined the two tissues, the endoderm induced the formation of mesoderm in the adjacent regions of the ectoderm.
Although scientists had tracked the fate of endoderm, investigated the ability of endodermal cells to differentiate, and examined the induction potential of endoderm cells, they did not investigate the molecular pathways that specify and configure endoderm until the 1990s.
From these studies emerged the theory that maternal cues, or developmental effects that the mother brings to the egg before fertilization, act through three main families of protein-encoding genes to help regulate early endoderm differentiation.
These signals are β-catenin, VegT, and Otx proteins. The molecular pathways involved in the later stages of endoderm differentiation and patterning are different between species, especially the transcription factors or proteins that help regulate gene expression.
GATA factors in particular are expressed in mesendoderm and are necessary for the endoderm to differentiate.
While there are some conserved genetic elements in the animal kingdom, such as β-catenin, some parts of the endoderm induction pathway, especially signals such as the Nodal and Wnt proteins, are specific to vertebrates.
In 2002, Eric Davidson and his colleagues at the California Institute of Technology in Pasadena, California, announced in their journal the complete network of genes that regulate the specification of endoderm and mesoderm in sea urchins: “A genomic regulatory network for the development”.
Davidson confirmed that network of genes in a collaborative paper published in 2012.