amniote Amniotes are a clade of tetrapod vertebrates that comprises sauropsids (including all reptiles and birds, and extinct parareptiles and non-avian dinosaurs) and synapsids (including pelycosaurs and therapsids such as mammals). They are disti ...

embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

, the epiblast (also known as the primitive ectoderm) is one of two distinct cell layers arising from the

inner cell mass The inner cell mass (ICM) or embryoblast (known as the pluriblast in marsupials) is a structure in the early development of an embryo. It is the mass of cells inside the blastocyst that will eventually give rise to the definitive structures of ...

in the

mammalian Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...

blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...

, or from the

blastula Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula (f ...

reptiles Reptiles, as most commonly defined are the animals in the Class (biology), class Reptilia ( ), a paraphyletic grouping comprising all sauropsid, sauropsids except birds. Living reptiles comprise turtles, crocodilians, Squamata, squamates (lizar ...

and

birds Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...

, the other layer is the

hypoblast In amniote embryology, the hypoblast, is one of two distinct layers arising from the inner cell mass in the mammalian blastocyst, or from the blastodisc in reptiles and birds. The hypoblast gives rise to the yolk sac, which in turn gives ris ...

. It derives the

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

proper through its differentiation into the three primary

germ layer A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three pr ...

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

and

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...

, during

gastrulation Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals the blastocyst is reorganized into a multilayered structure known as the gastrula. Be ...

. The amnionic ectoderm and extraembryonic mesoderm also originate from the epiblast. The other layer of the inner cell mass, the hypoblast, gives rise to the

yolk sac The yolk sac is a membranous sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''yolk sac'' is ...

, which in turn gives rise to the

chorion The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It develops from an outer fold on the surface of the yolk sac, which lies outside the zona pellucida (in mammals), known as the vitell ...

Discovery of the epiblast

The epiblast was first discovered by

Christian Heinrich Pander Heinz Christian Pander, also Christian Heinrich Pander ( – ), was a Russian Empire ethnic Baltic German biologist and embryologist. Biography In 1817 he received his doctorate from the University of Würzburg, and spent several years (1827� ...

(1794-1865), a Baltic German biologist and embryologist. With the help of anatomist

Ignaz Döllinger Ignaz Döllinger (27 May 1770 – 14 January 1841) was a German doctor, anatomist and physiologist and one of the first professors to understand and treat medicine as a natural science. Biography Ignaz Döllinger was born in 1770 in Bamberg, w ...

(1770–1841) and draftsman

Eduard Joseph d'Alton Joseph Wilhelm Eduard d’Alton (August 11, 1772 – May 11, 1840) was a German engraver and naturalist who was a native of Aquileia (today part of Italy). He was the father of anatomist Johann Samuel Eduard d'Alton (1803–1854). Originall ...

(1772-1840), Pander observed thousands of chicken eggs under a microscope, and ultimately discovered and described the chicken blastoderm and its structures, including the epiblast. He published these findings in Beiträge zur Entwickelungsgeschichte des Hühnchens im Eye. Other early embryologists that studied the epiblast and blastoderm include

Karl Ernst von Baer Karl Ernst Ritter von Baer Edler von Huthorn ( – ) was a Baltic German scientist and explorer. Baer was a naturalist, biologist, geologist, meteorologist, geographer, and is considered a, or the, founding father of embryology. He was ...

(1792-1876) and Wilhelm His (1831-1904).

Mammals

mammalian embryogenesis Mammalian embryogenesis is the process of cell division and cellular differentiation during early prenatal development which leads to the development of a mammalian embryo. Difference from embryogenesis of lower chordates Due to the fact that p ...

, differentiation and segregation of cells composing the inner cell mass of the blastocyst yields two distinct layers—the epiblast ("primitive ectoderm") and the

("primitive endoderm"). While the

cuboidal Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

hypoblast cells delaminate ventrally, away from the embryonic pole, to line the

blastocoele The blastocoel (), also spelled blastocoele and blastocele, and also called cleavage cavity, or segmentation cavity is a fluid-filled or yolk-filled cavity that forms in the blastula during very early embryonic development. At this stage in mammal ...

, the remaining cells of the inner cell mass, situated between the hypoblast and the polar

trophoblast The trophoblast (from Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the p ...

, become the epiblast and comprise

columnar cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

. In the mouse, primordial

germ cell Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embry ...

s are specified from epiblast cells. This specification is accompanied by extensive epigenetic reprogramming that involves global

DNA demethylation For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequenc ...

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

reorganization and imprint erasure leading to

totipotency Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...

. The DNA

base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...

pathway has a central role in the process of

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

-wide demethylation. Upon commencement of

, the

primitive streak The primitive streak is a structure that forms in the early embryo in amniotes. In amphibians the equivalent structure is the blastopore. During early embryonic development, the embryonic disc becomes oval shaped, and then pear-shaped with the ...

, a visible, morphological linear band of cells, appears on the posterior epiblast and orients along the anterior-posterior embryo axis. Initiated by signals from the underlying hypoblast, formation of the primitive streak is predicated on epiblast cell migration, mediated by

Nodal Nodal homolog is a secretory protein that in humans is encoded by the ''NODAL'' gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily (TGF-β superfamily). Like many other members of this superf ...

, from the lateral-posterior regions of the epiblast to the center midline. The

primitive node The primitive node (or primitive knot) is the organizer for gastrulation in most amniote embryos. In birds it is known as Hensen's node, and in amphibians it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in am ...

is situated at the anterior end of the primitive streak and serves as the organizer for gastrulation, determining epiblast cell fate by inducing the differentiation of migrating epiblast cells during gastrulation. During gastrulation, migrating epiblast cells undergo epithelial-mesenchymal transition in order to lose cell-cell adhesion (

E-cadherin Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the ''CDH1'' gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian ...

), delaminate from the epiblast layer and migrate over the dorsal surface of the epiblast then down through the primitive streak. The first wave of epiblast cells to invaginate through the primitive streak invades and displaces the hypoblast to become the embryonic endoderm. The mesoderm layer is established next as migrating epiblast cells move through the primitive streak then spread out within the space between the endoderm and remaining epiblast, which once the mesoderm layer has formed ultimately becomes the definitive ectoderm. The process of gastrulation results in a

trilaminar germ disc A trilaminar embryonic disc (or trilaminary blastoderm, or trilaminar germ disk) is an early stage in the development of triploblastic organisms, which include humans and many other animals. It is the next stage from the earlier bilaminar embryo ...

, consisting of the ectoderm, mesoderm and endoderm layers. Migration of epiblast cells in the mammalian embryo

Epiblast diversity

Epiblasts exhibit diverse structure across species as a result of early embryo morphogenesis. The human epiblast assumes a disc shape, conforming to the embryonic disc morphology; whereas, the mouse epiblast develops in a cup shape within the cylindrical embryo. During implantation of the blastocyst, both the human and mouse epiblasts form a rosette shape in a process called polarization. Polarization results from the interaction between the mammalian blastocyst and β1-integrin from the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

, produced from the extra-embryonic tissues. At this stage, both human and mouse epiblasts consist of a

pseudostratified columnar epithelium A pseudostratified epithelium is a type of epithelium that, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia. As it rarely occurs as squamous or cuboidal epithelia, ...

. Shortly after, the human epiblast will assume a disc shape while the amniotic cavity forms. The epiblast cells adjacent to the trophoblast are specified to become amnion cells. The mouse epiblast transitions from a rosette structure to a cup. A pro-amniotic cavity forms, surrounded by the epiblast cup fused to extraembryonic ectoderm. Mouse epiblast cells are not specified to amnion cell fate.

Birds

Gastrulation occurs in the epiblast of avian embryos. A local thickening of the epiblast, known as

Koller's sickle In avian gastrulation, Koller's sickle is a local thickening of cells at the posterior edge of the upper layer of the area pellucida called the epiblast. Koller's sickle is crucial for avian development, due to its critical role in inducing the di ...

, is key in inducing the primitive streak, the structure through which gastrulation occurs.Gilbert SF. Developmental Biology. 10th edition. Sunderland (MA): Sinauer Associates; 2014. Early Development in Birds. Print Studies on chick embryos have shown that mediolateral cell intercalation occurs before gastrulation. The intercalation event is guided by

fibroblast growth factors Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...

from the hypoblast. It is suggested that the evolution of the amniote primitive streak from the blastopore was due to the acquisition of the mediolateral intercalation event, which positions the primitive streak and acts independently of

mesendoderm Mesenchyme () is a type of loosely organized animal embryonic development, embryonic connective tissue of Cell differentiation, undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchym ...

formation.

Reptiles

Ancestors of

Amniotes Amniotes are a clade of tetrapod vertebrates that comprises sauropsids (including all reptiles and birds, and extinct parareptiles and non-avian dinosaurs) and synapsids (including pelycosaurs and therapsids such as mammals). They are distingu ...

(mammals, birds, reptiles) underwent

primarily by an infolding of the epiblast layer (

involution Involution may refer to: * Involute, a construction in the differential geometry of curves * '' Agricultural Involution: The Processes of Ecological Change in Indonesia'', a 1963 study of intensification of production through increased labour inpu ...

). Mammals and birds have evolved to rely on ingression during gastrulation where epiblast cells converge at the midline and ingress at the

. Reptile gastrulation differs slightly from birds and mammals. Reptiles exhibit bi-modal gastrulation during embryogenesis and lack a primitive streak. Bi-modal gastrulation is characterized by involution of the cells in the anterior and lateral regions of the blastopore and ingression of the cells of the blastopore plate in the posterior region. Analogies between the blastopore plate and primitive streak suggest the blastopore plate was a precursor to the mammalian and avian primitive streak.

References