In amniote

embryology Embryology (from Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, '' -logia'') is the branch of animal biology that studies the prenatal development of gametes (sex cells), fertilization, and development of embryos an ...

, the hypoblast, is one of two distinct layers arising from the inner cell mass in the

mammalian Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

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 th ...

, or from the

blastodisc The blastodisc, also called the germinal disc, is the embryo-forming part on the yolk of the egg of an animal that undergoes discoidal meroblastic cleavage. Discoidal cleavage occurs in those animals with a large proportion of yolk in their eggs, ...

reptiles Reptiles, as most commonly defined are the animals in the class Reptilia ( ), a paraphyletic grouping comprising all sauropsids except birds. Living reptiles comprise turtles, crocodilians, squamates (lizards and snakes) and rhynchocephali ...

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 lightweig ...

. 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 fa ...

, 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 vitellin ...

. The hypoblast is a layer of cells in fish and amniote embryos. The hypoblast helps determine the embryo's body axes, and its migration determines the cell movements that accompany the formation 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 ...

, and helps to orient the embryo, and create bilateral symmetry. The other layer of the inner cell mass, the

epiblast In amniote embryonic development, the epiblast (also known as the primitive ectoderm) is one of two distinct cell layers arising from the inner cell mass in the mammalian blastocyst, or from the blastula in reptiles and birds, the other layer ...

, differentiates 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 the o ...

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 Emb ...

, 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 ...

Structure

The hypoblast lies beneath the

and consists of small

cuboid In geometry, a cuboid is a hexahedron, a six-faced solid. Its faces are quadrilaterals. Cuboid means "like a cube", in the sense that by adjusting the length of the edges or the angles between edges and faces a cuboid can be transformed into a cu ...

al cells. The hypoblast in fish (but not in birds and mammals) contains the precursors of both the

and

. In birds and mammals, it contains precursors to the extraembryonic endoderm of the

. In chick embryos, early cleavage forms an area opaca and an area pellucida, and the region between these is called the marginal zone. Area opaca is the blastoderm's peripheral part where the cells remain unseparated from the yolk. It is a white area that transmits light.

Function

Although the hypoblast does not contribute to the embryo, it influences the orientation of the embryo. The hypoblast also inhibits primitive streak formation. The absence of hypoblast results in multiple

s in chicken embryos. The primitive endoderm derived yolk sac ensures the proper

organogenesis Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal ...

of the fetus and the exchange of nutrients, gases, and wastes. Hypoblast cells also provide chemical signals that specify the migration of epiblast cells.

Amniotes

Birds

In birds, the primitive streak formation is generated by a thickening of the epiblast called the

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 d ...

The Koller's sickle is created at the posterior edge of the area pellucida while the rest of the cells of the area pellucida remain at the surface, forming the epiblast. In chicks, the mesoderm cells don't invaginate, like in amphibians, but they migrate medially and

caudally Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

from both sides and create a midline thickening called primitive streak. The primitive streak grows rapidly in length as more presumptive mesoderm cells continue to aggregate inward.

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. ...

begins in the area pellucida next to the posterior marginal zone, as the hypoblast and primitive streak both start there. The avian embryo comes entirely from the epiblast, and the hypoblast does not contribute to any cells. The hypoblast cells form parts of the other membranes such as the yolk sac and the stalk linking the yolk mass to the endodermal digestive tube. In between the area opaca and Koller's sickle is a belt-like region called the

posterior marginal zone 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 d ...

(PMZ). The PMZ organizes the Hensen's center in amniotes. Meanwhile, cells in more anterior regions of the epiblast delaminate and stay attached to the epiblast to form hypoblast "islands." These islands are clusters of 5–20 cells that migrate and become the primary hypoblast. The sheet of cells that grows anteriorly from Koller's sickle combines with the primary hypoblast to form the secondary hypoblast (also called the endoblast). The resulting two-layered

blastoderm A blastoderm ( germinal disc, blastodisc) is a single layer of embryonic epithelial tissue that makes up the blastula. It encloses the fluid filled blastocoel. Gastrulation follows blastoderm formation, where the tips of the blastoderm begins the ...

(epiblast and hypoblast) is joined at the marginal zone of the area opaca, and the space between the layers forms a blastocoel-like a cavity. Cell division adds to the length produced by convergent extension. Some of the cells from the anterior portion of the epiblast contribute to the formation of Hensen's node. The Hensen's node is the organizer for

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. ...

in the vertebrate embryo. Simultaneously, the secondary hypoblast (endoblast) cells continue to migrate anteriorly from the blastoderm's posterior marginal zone. The elongation of the primitive streak is coextensive with the anterior migration of these secondary hypoblast cells, and the hypoblast directs the movement of the primitive streak. The streak eventually extends to about ¾ of the length of the area pellucida. Cells migrate to the primitive streak, and as they enter the embryo the cells separate into two layers. The deep layer joins the hypoblast along its midline, displacing the hypoblast cells to the sides. The first cells to migrate through Hensen's node are destined to become the foregut's pharyngeal endoderm. Once deep within the embryo, the endodermal cells migrate anteriorly and eventually displace the hypoblast cells, causing the hypoblast cells to be confined to a region in the area's anterior portion pellucida. This pattern appears similar to that of amphibian embryos. Nodal activity is needed to initiate the primitive streak, and that it is the secretion of Cerberus—an antagonist of Nodal—by the primary hypoblast cells that prevent primitive streak formation. As the primary hypoblast cells move away from the PMZ,

Cerberus In Greek mythology, Cerberus (; grc-gre, Κέρβερος ''Kérberos'' ), often referred to as the hound of Hades, is a multi-headed dog that guards the gates of the Underworld to prevent the dead from leaving. He was the offspring of the ...

protein is no longer present, allowing Nodal activity (and, therefore, forming the primitive streak) in the posterior epiblast. Once formed, however, the streak secretes its Nodal antagonist—the Lefty protein—which prevents further primitive streaks from forming. Eventually, the Cerberus-secreting hypoblast cells are pushed to the future anterior of the embryo, where they contribute to ensuring that neural cells in this region become forebrain rather than more posterior structures the nervous system. As the primitive streak reaches its maximum length, transcription of the Sonic hedgehog gene (Shh) becomes restricted to the embryo's left side, controlled by

activin Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...

and its receptor.

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 tha ...

, differentiation and segregation of cells in the inner cell mass of the blastocyst produces two different layers—the epiblast ("primitive ectoderm") and the hypoblast ("primitive endoderm"). The first segregation of cells within the inner cell mass forms two layers. In contact with the blastocoel, the lower layer is called the primitive endoderm, and it is homologous to the chick embryo hypoblast. While 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 pl ...

, become the epiblast. 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 from epiblast cells. This specification is accompanied by extensive

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are " ...

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 eukaryote, 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 ...

reorganization, and imprint erasure which results in totipotency. The mammalian equivalent to the chick hypoblast is called the anterior visceral endoderm (AVE) and creates an anterior region by secreting antagonists of Nodal. In the mouse, (the most studied mammalian model organism for this) the hypoblast restricts Nodal activity using Cerberus and Lefty1 while birds use only Cerberus.

Fish

In fish, the hypoblast is the inner layer of the thickened margin of the epibolizing blastoderm in the gastrulating fish embryo. The hypoblast in fish (but not in birds or mammals) contains the precursors of both the endoderm and mesoderm.

Genetics

The

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular ...

pathway, the Wnt pathway, is activated by fibroblast growth factors (FGF) produced by the hypoblast. If the hypoblast is rotated, the orientation of the primitive streak follows the rotation. If FGF signaling is activated in the epiblast margin, Wnt signaling will occur there. The orientation of the primitive streak will change as if the hypoblast had been placed there. The cell migrations that form the primitive streak appear to be regulated by FGFs from the hypoblast, which activates the Wnt planar cell polarity pathway in the epiblast. The Wnt pathway, in turn, is activated by FGFs produced by the hypoblast.

References

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