Gastrulation

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Gastrulation
blastula, made up of one layer, folds inward and enlarges to create a gastrula. This diagram is color-coded: ectoderm, blue; endoderm, green; blastocoel (the yolk sac), yellow; and archenteron (the primary gut), purple.
Identifiers
MeSHD054262
Anatomical terminology]

Gastrulation is the stage in the early

blastula (a single-layered hollow sphere of cells), or in mammals the blastocyst, is reorganized into a two-layered or three-layered embryo known as the gastrula.[1] Before gastrulation, the embryo is a continuous epithelial sheet of cells; by the end of gastrulation, the embryo has begun differentiation to establish distinct cell lineages, set up the basic axes of the body (e.g. dorsal–ventral, anterior–posterior), and internalized one or more cell types including the prospective gut.[2]

Gastrula layers

In

Sponges
do not go through the gastrula stage.

Gastrulation takes place after

organs develop within the newly formed germ layers.[6] Each layer gives rise to specific tissues
and organs in the developing embryo.

Following gastrulation, cells in the body are either organized into sheets of connected cells (as in

epithelia), or as a mesh of isolated cells, such as mesenchyme.[4][8]

Basic cell movements

Although gastrulation patterns exhibit enormous variation throughout the animal kingdom, they are unified by the five basic types of cell movements that occur during gastrulation:[2][9]

  1. Invagination
  2. Involution
  3. Ingression
  4. Delamination
  5. Epiboly

Etymology

The terms "gastrula" and "gastrulation" were coined by Ernst Haeckel, in his 1872 work "Biology of Calcareous Sponges".[10] Gastrula (literally, "little belly") is a neo-Latin diminutive based on the Ancient Greek γαστήρ gastḗr ("a belly").

Importance

Lewis Wolpert, pioneering developmental biologist in the field, has been credited for noting that "It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life."[2][11]

A description of the gastrulation process in a human embryo in three dimensions

Model systems

Gastrulation is highly variable across the animal kingdom but has underlying similarities. Gastrulation has been studied in many animals, but some models have been used for longer than others. Furthermore, it is easier to study development in animals that develop outside the mother.

mollusc, sea urchin, frog, and chicken. A human model system is the gastruloid
.

Protostomes versus deuterostomes

The distinction between protostomes and deuterostomes is based on the direction in which the mouth (stoma) develops in relation to the blastopore. Protostome derives from the Greek word protostoma meaning "first mouth" (πρῶτος + στόμα) whereas Deuterostome's etymology is "second mouth" from the words second and mouth (δεύτερος + στόμα).[citation needed]

The major distinctions between deuterostomes and protostomes are found in

embryonic development
:

Sea urchins

Sea urchins have been important model organisms in developmental biology since the 19th century.[12] Their gastrulation is often considered the archetype for invertebrate deuterostomes.[13] Experiments along with computer simulations have been used to gain knowledge about gastrulation in the sea urchin. Recent simulations found that planar cell polarity is sufficient to drive sea urchin gastrulation.[14]

Germ layer determination

Sea urchins exhibit highly stereotyped cleavage patterns and cell fates. Maternally deposited

mRNAs establish the organizing center of the sea urchin embryo. Canonical Wnt and Delta-Notch signaling progressively segregate progressive endoderm and mesoderm.[15]

Cell internalization

In

vegetal pole, which contribute approximately 30% to the final archenteron length. The gut's final length depends on cell rearrangements within the archenteron.[16]

Amphibians

The frog genus Xenopus has been used as a model organism for the study of gastrulation.[17]

Symmetry breaking

The sperm contributes one of the two

organizer. Thus, the area on the vegetal side opposite the sperm entry point will become the organizer.[18] Hilde Mangold, working in the lab of Hans Spemann, demonstrated that this special "organizer" of the embryo is necessary and sufficient to induce gastrulation.[19][20][21]

Germ layer determination

Specification of endoderm depends on rearrangement of maternally deposited determinants, leading to nuclearization of

Beta-catenin. Mesoderm is induced by signaling from the presumptive endoderm to cells that would otherwise become ectoderm.[18]

Cell internalization

The dorsal lip of the blastopore is the mechanical driver of gastrulation. The first sign of invagination seen in the frog is the dorsal lip.[citation needed]

Cell signaling

In the frog, Xenopus, one of the signals is retinoic acid (RA).[22] RA signaling in this organism can affect the formation of the endoderm and depending on the timing of the signaling, it can determine the fate whether its pancreatic, intestinal, or respiratory. Other signals such as Wnt and BMP also play a role in respiratory fate of the Xenopus by activating cell lineage tracers.[22]

Amniotes

Overview

In

germ layers.[7]

Symmetry breaking

In preparation for gastrulation, the embryo must become asymmetric along both the

nodal signaling.[7]

mesenchymal
cell.

Germ layer determination

The

nodal signaling.[25] The region defined as the primitive streak continues to grow towards the distal tip.[7]

During the early stages of development, the primitive streak is the structure that will establish

beta-catenin
is critical to the proper formation of the organizer region that is responsible for initiating gastrulation.

Cell internalization

In order for the cells to move from the

FGF8 is implicated in the process of this dispersal from the primitive streak.[25]

Cell signaling

There are certain signals that play a role in determination and formation of the three germ layers, such as FGF, RA, and Wnt.[22] In mammals such as mice, RA signaling can play a role in lung formation. If there is not enough RA, there will be an error in the lung production. RA also regulates the respiratory competence in this mouse model.[citation needed]

Cell signaling driving gastrulation

During gastrulation, the cells are differentiated into the ectoderm or

β-catenin plays a key role in nodal signaling and endoderm formation.[31] Fibroblast growth factors (FGF), canonical Wnt pathway, bone morphogenetic protein (BMP), and retinoic acid (RA) are all important in the formation and development of the endoderm.[22] FGF are important in producing the homeobox gene which regulates early anatomical development. BMP signaling plays a role in the liver and promotes hepatic fate. RA signaling also induce homeobox genes such as Hoxb1 and Hoxa5. In mice, if there is a lack in RA signaling the mouse will not develop lungs.[22] RA signaling also has multiple uses in organ formation of the pharyngeal arches, the foregut, and hindgut.[22]

Gastrulation in vitro

There have been a number of attempts to understand the processes of gastrulation using in vitro techniques in parallel and complementary to studies in embryos, usually though the use of 2D[32][33][34] and 3D cell (Embryonic organoids) culture techniques[35][36][37][38] using embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs). These are associated with number of clear advantages in using tissue-culture based protocols, some of which include reducing the cost of associated in vivo work (thereby reducing, replacing and refining the use of animals in experiments; the 3Rs), being able to accurately apply agonists/antagonists in spatially and temporally specific manner[36][37] which may be technically difficult to perform during Gastrulation. However, it is important to relate the observations in culture to the processes occurring in the embryo for context.

To illustrate this, the guided differentiation of mouse ESCs has resulted in generating

brachyury up regulation and the cellular changes associated with an epithelial to mesenchymal transition[32]), and human ESCs cultured on micro patterns, treated with BMP4, can generate spatial differentiation pattern similar to the arrangement of the germ layers in the human embryo.[33][34] Finally, using 3D embryoid body- and organoid-based techniques, small aggregates of mouse ESCs (Embryonic Organoids, or Gastruloids) are able to show a number of processes of early mammalian embryo development such as symmetry-breaking, polarisation of gene expression, gastrulation-like movements, axial elongation and the generation of all three embryonic axes (anteroposterior, dorsoventral and left-right axes).[35][36][37][39]

In vitro fertilization occurs in a laboratory. The process of in vitro fertilization is when mature eggs are removed from the ovaries and are placed in a cultured medium where they are fertilized by sperm. In the culture the embryo will form.[40] 14 days after fertilization the primitive streak forms. The formation of the primitive streak has been known to some countries as "human individuality".[41] This means that the embryo is now a being itself, it is its own entity. The countries that believe this have created a 14-day rule in which it is illegal to study or experiment on a human embryo after the 14-day period in vitro. Research has been conducted on the first 14 days of an embryo, but no known studies have been done after the 14 days.[42] With the rule in place, mice embryos are used understand the development after 14 days; however, there are differences in the development between mice and humans.

See also

References

Notes

Bibliography

Further reading

External links