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 two-layered or three-layered embryo known as the gastrula.
Gastrula layers
In
Triploblasty organisms, the gastrula is trilaminar (three-layered). These three
germ layers are the
ectoderm (outer layer),
mesoderm (middle layer), and
endoderm (inner layer).
[Mundlos 2009: p. 422][McGeady, 2004: p. 34] In
Diploblasty organisms, such as
Cnidaria and
Ctenophora, the gastrula has only ectoderm and endoderm. The two layers are also sometimes referred to as the
hypoblast and
epiblast.
do not go through the gastrula stage.
Gastrulation takes place after cleavage and the formation of the blastula, or blastocyst. Gastrulation is followed by organogenesis, when individual organs develop within the newly formed germ layers.[Hall, 1998: pp. 132-134] Each layer gives rise to specific tissues and organs in the developing embryo.
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The ectoderm gives rise to epidermis, the nervous system, and to the neural crest in vertebrates.
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The endoderm gives rise to the epithelium of the Digestion and respiratory system, and organs associated with the digestive system, such as the liver and pancreas.
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The mesoderm gives rise to many cell types such as muscle, bone, and connective tissue. In vertebrates, mesoderm derivatives include the notochord, the heart, blood and blood vessels, the cartilage of the ribs and vertebrae, and the dermis.
[Arnold & Robinson, 2009]
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.
[Hall, 1998: p. 177]
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:
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Invagination
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Involution
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Ingression
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Delamination
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Epiboly
Etymology
The terms "gastrula" and "gastrulation" were coined by
Ernst Haeckel, in his 1872 work
"Biology of Calcareous Sponges".
[Ereskovsky 2010: p. 236]
Gastrula (literally, "little belly") is a neo-Latin diminutive based on the Ancient Greek γαστήρ
("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."
[Lewis Wolpert (2008) The triumph of the embryo. Courier Corporation, page 12. ]
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.
whose gastrulation is understood in the greatest detail include the
mollusc,
sea urchin,
frog, and
chicken. A human model system is the
gastruloid.
Protostomes versus deuterostomes
The distinction between
and
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).
The major distinctions between deuterostomes and protostomes are found in embryonic development:
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Mouth/anus
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In protostome development, the first opening in development, the blastopore, becomes the animal's mouth.
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In deuterostome development, the blastopore becomes the animal's anus.
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Cleavage
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have what is known as spiral cleavage which is determinate, meaning that the fate of the cells is determined as they are formed.
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have what is known as radial cleavage that is indeterminate.
Sea urchins
have been important
in developmental biology since the 19th century.
[Laubichler, M.D. and Davidson, E. H. (2008). "Boveri's long experiment: sea urchin merogones and the establishment of the role of nuclear chromosomes in development". Developmental Biology. 314(1):1–11. .] Their gastrulation is often considered the archetype for invertebrate deuterostomes.
Sea urchins exhibit highly stereotyped cleavage patterns and cell fates. Maternally deposited establish the organizing center of the sea urchin embryo. Canonical Wnt and Delta-Notch signaling progressively segregate progressive endoderm and mesoderm.[McClay, D. R. 2009. Cleavage and Gastrulation in Sea Urchin. eLS. ]
The first cells to internalize are the primary mesenchyme cells (PMCs), which have a skeletogenic fate, which ingress during the blastula stage. Gastrulation – internalization of the prospective endoderm and non-skeletogenic mesoderm – begins shortly thereafter with invagination and other cell rearrangements the vegetal pole, which contribute approximately 30% to the final archenteron length. The gut's final length depends on cell rearrangements within the archenteron.
Amphibians
The
frog genus Xenopus has been used as a
model organism for the study of gastrulation.
Symmetry breaking
The sperm contributes one of the two mitotic asters needed to complete first cleavage. The sperm can enter anywhere in the
animal pole of the egg but its exact point of entry will break the egg's radial symmetry by organizing the
cytoskeleton. Prior to first cleavage, the egg's cortex rotates relative to the internal
cytoplasm by the coordinated action of
microtubules, in a process known as cortical rotation. This displacement brings maternally loaded determinants of cell fate from the equatorial cytoplasm and vegetal cortex into contact, and together these determinants set up the
Primitive knot. Thus, the area on the vegetal side opposite the sperm entry point will become the organizer.
, working in the lab of
Hans Spemann, demonstrated that this special "organizer" of the embryo is necessary and sufficient to induce gastrulation.
The dorsal lip of the blastopore is the mechanical driver of gastrulation, and the first sign of invagination seen in the frog.
Germ layer differentiation
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.
Cell signaling
In the frog,
Xenopus, one of the signals is
retinoic acid (RA).
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.
Amniotes
Overview
In
(reptiles, birds and mammals), gastrulation involves the creation of the blastopore, an opening into the
archenteron. Note that the blastopore is not an opening into the
blastocoel, the space within the
blastula, but represents a new inpocketing that pushes the existing surfaces of the blastula together. In
amniotes, gastrulation occurs in the following sequence: (1) the
embryo becomes
asymmetry; (2) the
primitive streak forms; (3) cells from the
epiblast at the
primitive streak undergo an epithelial to mesenchymal transition and ingress at the
primitive streak to form the
germ layers.
Symmetry breaking
In preparation for gastrulation, the embryo must become asymmetric along both the proximal-distal axis and the anteroposterior axis. The proximal-distal axis is formed when the cells of the embryo form the "egg cylinder", which consists of the extraembryonic tissues, which give rise to structures like the
placenta, at the proximal end and the
epiblast at the distal end. Many signaling pathways contribute to this reorganization, including BMP, FGF,
nodal signaling, and Wnt. Visceral endoderm surrounds the
epiblast. The distal visceral endoderm (DVE) migrates to the
anterior portion of the embryo, forming the anterior visceral endoderm (AVE). This breaks anterior-posterior symmetry and is regulated by
NODAL signaling.
Germ layer determination
The
primitive streak is formed at the beginning of gastrulation and is found at the junction between the extraembryonic tissue and the
epiblast on the posterior side of the embryo and the site of ingression.
[Tam & Behringer, 1997] Formation of the
primitive streak is reliant upon
NODAL signaling
in the Koller's sickle within the cells contributing to the primitive streak and BMP4 signaling from the extraembryonic tissue.
[Catala, 2005: p. 1535] Furthermore, Cer1 and Lefty1 restrict the primitive streak to the appropriate location by antagonizing
NODAL signaling.
The region defined as the
primitive streak continues to grow towards the distal tip.
During the early stages of development, the primitive streak is the structure that will establish bilateral symmetry, determine the site of gastrulation and initiate germ layer formation.
Cell internalization
In order for the cells to move from the
epithelium of the
epiblast through the
primitive streak to form a new layer, the cells must undergo an epithelial to mesenchymal transition (EMT) to lose their epithelial characteristics, such as
Cell adhesion. FGF signaling is necessary for proper EMT. FGFR1 is needed for the up regulation of SNAI1, which down regulates E-cadherin, causing a loss of cell adhesion. Following the EMT, the cells ingress through the
primitive streak and spread out to form a new layer of cells or join existing layers. FGF8 is implicated in the process of this dispersal from the
primitive streak.
Cell signaling driving gastrulation
During gastrulation, the cells are differentiated into the ectoderm or
mesendoderm, which then separates into the mesoderm and endoderm.
The endoderm and mesoderm form due to the
nodal signaling. Nodal signaling uses ligands that are part of TGFβ family. These ligands will signal transmembrane serine/threonine kinase receptors, and this will then phosphorylate Smad2 and Smad3. This protein will then attach itself to Smad4 and relocate to the nucleus where the mesendoderm genes will begin to be transcribed. The Wnt pathway along with
Beta-catenin plays a key role in nodal signaling and endoderm formation.
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.
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.
RA signaling also has multiple uses in organ formation of the pharyngeal arches, the foregut, and hindgut.
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
Cell culture and 3D cell (
Gastruloid) culture techniques
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
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 primitive streak–like cells that display many of the characteristics of epiblast cells that traverse through the primitive streak
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.
See also
Notes
Bibliography
Further reading
External links
