Classic model systemsGastrulation 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. Animals whose gastrulation is understood in the greatest detail include: *Mollusc *Sea urchin *Frog *Chicken
Protostomes versus deuterostomesThe Embryological origins of the mouth and anus, 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). The major distinctions between deuterostomes and protostomes are found in : * Mouth/anus ** In protostome development, the first opening in development, the blastopore, becomes the animal's mouth. ** In deuterostome development, the blastopore becomes the animal's anus. * Cleavage (embryo), Cleavage ** Protostomes have what is known as ''Cleavage (embryo), spiral cleavage'' which is ''determinate'', meaning that the fate of the cells is determined as they are formed. ** Deuterostomes have what is known as ''Cleavage (embryo), radial cleavage'' that is ''indeterminate''.
Sea urchinsSea urchins Euechinoidea have been an important model system in developmental biology since the 19th century. Their gastrulation is often considered the archetype for invertebrate deuterostomes. Experiments along with computer simulations have been used to gain knowledge about gastrulation in Sea urchin. Recent simulations found that planar cell polarity is sufficient to drive Sea urchin gastrulation.
Germ layer determinationSea urchins exhibit highly stereotyped cleavage patterns and cell fates. Maternally deposited mRNAs establish the organizing center of the sea urchin embryo. Canonical Wnt signaling pathway, Wnt and Notch signaling pathway, Delta-Notch signaling progressively segregate progressive endoderm and mesoderm.
Cell internalizationIn sea urchins the first cells to internalize are the primary mesenchyme cells (PMCs), which have a Sea urchin skeletogenesis, 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. Th
AmphibiansThe frog, ''Xenopus'' has been used as a model organism for the study of gastrulation.
Symmetry breakingThe sperm contributes one of the two Spindle apparatus, mitotic asters needed to complete first cleavage. The sperm can enter anywhere in the animal half 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, organizer. Thus, the area on the vegetal side opposite the sperm entry point will become the organizer. Hilde Mangold, working in the lab of Hans Spemann, demonstrated that this special "organizer" of the embryo is Necessity and sufficiency, necessary and sufficient to induce gastrulation.
Germ layer determinationSpecification of endoderm depends on rearrangement of maternally deposited determinants, leading to nuclearization of Beta-catenin. Mesoderm is Cellular differentiation, induced by signaling from the presumptive endoderm to cells that would otherwise become ectoderm.
Cell internalizationThe dorsum (anatomy), dorsal lip of the blastopore is the mechanical driver of gastrulation. The first sign of invagination seen i
Cell signalingIn 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.
OverviewIn amniotes (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 , 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, asymmetric; (2) the primitive streak forms; (3) cells from the epiblast at the primitive streak undergo an Epithelial-mesenchymal transition, epithelial to mesenchymal transition and ingression (biology), ingress at the primitive streak to form the germ layers.
Symmetry breakingIn preparation for gastrulation, the embryo must become asymmetric along both the Proximo-distal, proximal-distal axis and the Anteroposterior, anterior-posterior 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 bone morphogenetic protein, BMP, fibroblast growth factor, FGF, nodal signaling, nodal, and Wnt signaling pathway, Wnt. Visceral endoderm surrounds the epiblast. The Anatomical terms of location#Proximal and distal, 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, nodal signaling.
Germ layer determinationThe 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 (biology), ingression.Tam & Behringer, 1997 Formation of the primitive streak is reliant upon NODAL, nodal signaling in the Koller's sickle within the cells contributing to the primitive streak and BMP4 signaling from the extraembryonic tissue.Catala, 2005
Cell internalizationIn 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-mesenchymal transition, epithelial to mesenchymal transition (EMT) to lose their epithelial characteristics, such as Cell adhesion, cell-cell adhesion. fibroblast growth factor, FGF signaling is necessary for proper EMT. FGFR1 is needed for the up regulation of SNAI1, which down regulates CDH1 (gene), E-cadherin, causing a loss of cell adhesion. Following the EMT, the cells ingression (biology), 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 signalingThere are certain signals that play a role in determination and formation of the three germ layers, such as FGF, RA, and Wnt. In mammals such as mice, RA signaling can play a role in lung formation. If there isn't enough RA, there will be an error in the lung production. RA also regulates the respiratory competence in this mouse model.
Cell signaling driving gastrulationDuring 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 Transforming growth factor beta, TGFβ family. These ligands will signal transmembrane serine/threonine kinase receptors, and this will then phosphorylate Mothers against decapentaplegic homolog 2, Smad2 and Mothers against decapentaplegic homolog 3, Smad3. This protein will then attach itself to Mothers against decapentaplegic homolog 4, Smad4 and relocate to the nucleus where the mesendoderm genes will begin to be transcribed. The Wnt signaling pathway, Wnt pathway along with Beta-catenin, β-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 won't 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, 2D and 3D cell (Gastruloid, Embryonic organoids) 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; Three Rs (animal research), 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 (e.g. transient brachyury up regulation and the cellular changes associated with an Epithelial–mesenchymal transition, epithelial to mesenchymal transition), and human ESCs cultured on micro patterns, treated with Bone morphogenetic protein 4, BMP4, can generate spatial differentiation pattern similar to the arrangement of the germ layers in the human embryo. Finally, using 3D embryoid body- and organoid-based techniques, small aggregates of mouse ESCs (Gastruloid, 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).
See also*Blastocyst * Deuterostome * Fate mapping * Primitive knot * Invagination * Neurulation * Protostome * Vegetal rotation
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