Gastrulation: Stages, Types, and Disorders in Embryonic Development
Gastrulation
In the third week of intrauterine life, the process of gastrulation is triggered. Through cell movements and hierarchical integrated holders, gastrulation achieves the goal of rearranging the cellular compartments of the bilaminar germ disc. At this stage, the gastrula stage, cells in the mesodermal compartment migration acquire new positions to establish the basic body plan with the formation of a trilaminar embryonic disc. This also defines and allows specific molecular interactions between the embryonic tissues.
The achievement of migration and invagination of the mesoderm into its final position depends on the formation of three structures: the primitive streak, Hensen’s knot, and the precordal plate. The first two structures depend on the mesoderm, while the last one depends on the endoderm. All three have, through their molecular products, a regulatory role on mesoderm invagination and initial differentiation: chordal mesoderm or notochord, lateral mesoderm, and pluripotential cardiogenic mesoderm. The primitive streak and Hensen’s knot, through their products, regulate the formation of the left-right axis on two levels: globally, for all organs and structures (lateral provision), and on a specific national level for the elements of asymmetrical arrangement.
Gastrulation
Gastrulation is a stage of embryonic development that occurs after the formation of the blastula, following segmentation or cleavage. It aims to form the fundamental layers of the embryo (germ layers). This process involves cell movements and migration, leading to the generation of three blastoderm layers. These early cell movements of gastrulation are similar in all animals, but gastrulation mechanisms are highly dependent on the amount of yolk available. Cell movements enable the contact of previously distant cells, allowing the inductive interactions that determine neurulation and organogenesis. The paternal genome begins to express itself. Gastrulation occurs between days 15 to 17, starting with the formation of the primitive streak or line.
The primitive streak is formed on the surface of the epiblast, opposite the precordal plate, at the caudal end of the embryo. It results from a thickening of the epiblast due to the proliferation and migration of epiblast cells towards the midplane of the embryonic disk. The primitive streak extends cranially and forms a bulge at its cranial end: the primitive node (or Hensen’s node). Simultaneously, a groove develops along the primitive streak: the primitive groove. This groove becomes more evident at the primitive streak, forming a depression: the primitive pit. The appearance of the primitive streak determines the identification of:
- The cranio-caudal axis.
- The cranial and caudal ends of the embryo.
- Its dorsal and ventral surfaces.
- Left and right sides.
These are established by both levels of body asymmetry. The primitive groove and pit result from the ventral (inward) invagination of epiblast cells.
As the epiblast cells invaginate, they will continue on well-established paths in the cranial and lateral directions. Epiblast cells that reach the hypoblast layer get between its cells and move to the suburbs, forming the roof of the yolk sac and the definitive endoderm. Moreover, other epiblast cells form a loose network of embryonic tissue called mesenchyme or mesoblast, which will result in the definitive mesoderm. Some mesenchymal cells reach the lateral edges of the mesoderm, contributing to the formation of extraembryonic mesoderm. Epiblast cells that enter the primitive streak and follow a cranial direction up to the precordal plate stop there, forming a cellular cord called the notochord process. Epiblast cells arising from this layer will form the ectoderm. The migration of epiblast cells to form the mesenchyme reaches the entire surface of the embryonic disk, except for the precordal plate or oropharyngeal membrane and a small area caudal to the primitive streak: the cloacal membrane.
This gastrulation process determines the change from a bilaminar embryonic disc to a trilaminar embryonic disc, with its three blastoderm layers: ectoderm, mesoderm, and endoderm.
During the 4th week, the primitive streak decreases in relative size, eventually disappearing at the end of the week. The failure of the primitive streak to involute leads to the formation of a large tumor at the sacral level, known as sacrococcygeal teratoma. At this stage, we can identify specific areas of cells “determined” to form a particular type of tissue.
In vertebrates, the gastrulation stage is followed by neurulation.
Germinative Layers
Gastrulation is intussusception: a wall of the blastula sinks toward the opposite wall, resulting in:
- Reduction of the blastula cavity (blastocoel).
- Formation of two walls in the embryo or embryonic layers (ectoderm and endoderm).
- Formation of a new cavity (limited by the endoderm) called the archenteron, which communicates with the exterior through the blastopore.
Mesoderm and Coelom Formation
With gastrulation, the embryo becomes diploblastic (with two embryonic layers: ectoderm and endoderm). The development of some animals does not pass the diploblasty state (examples are the sponges and cnidarians). But in the remaining animals, a third germ layer develops between the ectoderm and the endoderm: the mesoderm, in which the coelom or coelomic cavity is formed. These are called triploblastic or coelomates.
The formation of mesoderm and coelom may occur by three processes:
- Enterocoelous: From the sides of the archenteron and at the expense of the endoderm (types of gastrulation by invagination, as in echinoderms and amphioxus).
- Schizocoelous: At the expense of two bodies of blastomeres that form at the boundary between ectoderm and endoderm around the blastopore (in total and unequal egg segmentation, as in mollusks and annelids).
- Immigration: Proliferating cells at the edges or lips of the blastopore migrate to lie between the ectoderm and endoderm in the dorsal part of the latter. Thus, two lateral strands are split transversely into several segments or somites. The coelom is caused by the hollowing of the cell cords. This process occurs in vertebrates.
Organogenesis
Organogenesis is the third stage of embryonic development. It involves the formation of various organs from each of the embryonic layers. We can distinguish the following organs and tissues:
Derivatives of the Ectoderm
- The epidermis and glands attached to it (such as sweat glands), and mucous membranes of the body’s natural openings (mouth, nostrils, etc.).
- The central nervous system (formed by the thickening and collapse of the longitudinal midline of the ectoderm: ventral in invertebrates and dorsal in vertebrates).
Derivatives of the Endoderm
- The gut and its attached glands.
- The inner lining of some organs, like the lungs.
Derivatives of the Mesoderm
- The dermal layer of the skin and connective tissue elsewhere in the body.
- The circulatory system.
- The excretory system and gonads.
- The muscular system.
- The skeleton of chordates.
Sequence
Mitosis and Cell Migration
Once the blastula is formed, there is a displacement of surface cells into the blastocoel. This generates invagination and consequent shrinkage of the blastocoel cavity. This is accomplished by cells entering (which initially could be attributed ectodermal features) through the blastopore, in a move similar to turning over a sock. The point of entry of these cells forms an opening called the blastopore. While the blastocoel cavity decreases, a new cavity arises called the gastrocoel or archenteron, which will later become the gut. Mitotic activity, intense along the segmentation, decreases steadily while never completely ceasing.
Types of Cellular Segregation
The blastomeres, or groupings of them, undertake considerable migrations originating from cell segregation into two types, one of which will cover the other. The outer layer, or ectoblast (ectoderm), covers the inner layer or endoblast (endoderm). But the diploblastic gastrula is not only found in the Porifera and coelenterates (cnidarians and ctenophores); in all other metazoans, a middle layer or mesoblast (mesoderm) is sandwiched between the two layers above.
Formation of the Gastrula
In the blastula, a part of the blastomeres begins to invaginate, forming the blastopore. The place where this occurs is regulated genetically. The invagination progresses and invades all parts of the blastocoel, being scaled viewing the archenteron. The increased or new cavity is formed, which has the distinction of being in contact with the outside through the blastopore.
At this stage, the embryo is called a gastrula and gives rise to the layers of the embryo described above. Through the process of gastrulation, two layers of blastomeres have formed: one in contact with the exterior or ectoderm, and the other in contact with the archenteron or endoderm, and between the two, the blastocoel with the blastocoel fluid.
Types of Gastrulation
The process of gastrulation occurs differently depending on the egg and its subsequent segmentation. The main types of gastrulation are:
Gastrulation by Epiboly
Higher cells divide, spread, and slip, forming the embryo. It occurs when the egg has a moderate amount of yolk located in the vegetative pole, and the segmentation produces large yolk macromeres. In this case, the blastocoel is more or less virtual (stereoblastula), and intussusception is difficult because the vegetative pole macromeres have no mobility.
For this reason, micromeres located at the animal pole divide, proliferate, sink, and surround macromeres until the blastopore is formed in the vegetative pole.
They move the animal pole macromeres, which multiply by mitosis and move, involving the macromeres. You can get two results:
- The micromeres fail to stick together in the vegetative pole. In the gastrula, the outer cell layer (micromeres) will be the ectoderm, and the inner cells (macromeres) will be the endoderm. They have a small archenteron, but the blastopore disappears, and the blastocoel remains.
- The micromeres join in the vegetative pole; the germ layers are the same, but there is no archenteron or blastocoel. The animal will have a complete digestive tract, but it is formed in later stages.
Gastrulation in Amphibians
The eggs of amphibians are often yolk-laden with bilateral symmetry. The yolk-rich vegetative half is called white. Peripherally, the animal has a lightly pigmented brown yolk. The blastula formed after segmentation is a blastula with a small, displaced blastocoel, as the wall has at least two layers of cells, being considerably higher in the vegetal hemisphere. These cells prevent complete invagination during gastrulation. Morphogenetic movements of gastrulation begin with the appearance of the gray crescent. It starts in the back of the vitelline field.
Gastrulation begins with invagination and continues through a process of involution in the range of the gray crescent. Intussusception of migrating cells forms the archenteron. The notch that distinguishes the blastopore is now called the dorsal blastopore lip. These movements are known to occur around the entire embryo. While such movements of invagination and involution continue, the epiboly of germ ring cells eventually isolates the yolk cells within the limits of the blastopore, in an area known as the yolk plug.
The blastopore is now surrounded by dorsal, ventral, and lateral lips. The growing layer of cells that forms the roof of the archenteron gives rise to the endoderm and mesoderm, whereas, for some time, the floor of the archenteron will be occupied by large yolk cells. The cells of the outer surface of the embryo are now the ectoderm. As gastrulation proceeds, the ventral lip of the blastopore begins to involute, and the gradually invaginated endoderm proliferates to close the tip and complete the archenteron. The third layer, the mesoderm, develops between the endoderm and ectoderm.
During primary neurulation, the embryo within the primitive gut endoderm is surrounded by cells, and they are located around the mesoderm. In the dorsal midline, the notochord is transformed into a rod around which the mesoderm thickens to form the somites. In the ectodermal layer, nervous system cells begin to organize. The edges of the neural plate elevate and form a neural fold, a longitudinal elevation of the neural groove. The edges rise and unite in the midline to form a complete neural tube, which begins forming in the upper levels of the spinal cord and closes towards the caudal end. At this point, a new group of ectodermal cells begins to differentiate between the neural tube and ectoderm, forming the neural crest.
Gastrulation in Annelids
Approximately 15,000 species of annelids exist, including marine, freshwater, and terrestrial varieties. They range from 1 mm to 7 m in length and have variable coloration. Their bodies are metamerized, meaning there is a linear repetition of parts throughout the body due to the segmentation of the mesoderm. Annelids have three main parts: the prostomium (anterior, preoral, not a segment), the metastomium (set of all segments, the first being the peristome), and the pygidium (posterior to the anus, not a segment). The formation of terminal segments is…
Gastrulation by Emboly
By Invagination
Coeloblastulae have a central blastocoel. Vegetative pole cells fold inward and are introduced into the blastocoel by a process called intussusception. This creates a cavity surrounded by ectoderm called the archenteron, which will be the future digestive tract. The entrance pore is called the blastopore. Depending on subsequent development, the blastopore will lead to the anus, mouth, or close.
Two germ layers are formed: the outer layer is the ectoderm (epithelium, leading to the body surface and the nervous system), and the innermost, which lines the archenteron, is the endoderm (which forms the lining of the digestive tract). The outgrowths of the archenteron form the mesoderm (the third layer to form, giving rise to embryonic muscle and the reproductive system).
Most animal phyla have holoblastic segmentation, and in this case, the blastula looks like a hollow ball (coeloblastula) that delimits the cavity called the blastocoel. Such a blastula undergoes gastrulation by invagination, meaning that part of the ectodermal cells invaginates into the blastocoel to form the second germ layer (endoderm) and define a new cavity, the archenteron, which communicates with the exterior through the blastopore. This is the kind that has been detailed in the “Sequence” section.
Gastrulation in Fish
At the edges of the blastodisc on the yolk, epiboly occurs. This will also produce an involution at this edge that will affect the deep blastomeres. Thus, the embryo is defined by the epiblast and hypoblast, forming a germ ring around the blastodisc.
Simultaneously, there will be a convergence of blastomeres to the area of the disc, forming the embryonic shield, where the embryo develops with an anteroposterior axis.
In amphibians, the yolk plug cells were yolk-rich and vegetal. The epiboly continues until the yolk is completely covered. At the end, the yolk plug is formed, composed exclusively of yolk.
By Involution
Involution is a step-by-cell process from the outside through a fold. When the amount of egg yolk is so large that the segmentation is meroblastic, a small cap of cells or discoblastula forms, and gastrulation usually occurs by involution. This process involves cells at the periphery of the disc sinking back beneath the surface layer and forming a double layer. This is the typical case in cephalopods. The record of animal pole cells multiplying and forming another layer inside. The embryo has ectoderm and endoderm but nothing more.
Involution in Amphibians
Dorsal Lip Involution and Lateral Cell Epiboly: After dorsal lip involution, cells are constantly changing. The first involuting cells give rise to the pharynx, and the others give rise to notochord cells (chordamesoderm). Bottle cells invaginate but do not regress. Other mesodermal cells involute close by. With regression, the archenteron is forming, which displaces the blastocoel, extending it to one end of the blastula. The archenteron will be lined with endodermal cells.
By Delamination
Delamination is the formation of two layers from a single cellular sheet. It is a rare type of gastrulation. It also happens when a stereoblastula forms. The endoderm is formed from ectodermal cell division, migration, and subsidence. Gastrulation is completed with the separation of two layers of cells, an external and an internal one. There is no blastopore, but the archenteron cavity opens through a secondary process. This type of gastrulation is characteristic of coelenterates. Through mitosis, coeloblastula cells are separated into two layers. The mitotic spindles are radial, and segmentation planes occur parallel to the surface of the egg. The monolayer blastula becomes a double germ cell layer, forming an ectoderm and endoderm. The latter surrounds the archenteron, which is left as a remnant of the blastocoel. There is no blastopore. A gap should open, but secondarily, it is not comparable with the blastopore. In animals with this type of archenteron, another primary cavity will secrete a gelatinous substance between the endoderm and ectoderm, forming a structure called the mesoglea, full of cells that can pass through it (cnidarians).
Internal Migration or Immigration
In gastrulation by internal migration and immigration, some cells of the blastoderm will detach and grow in depth, initially forming a mass called the parenchyma. These cells give rise to the endoderm and ectoderm. This internal migration can start from a single point of the blastoderm (unipolar immigration) or from two or more areas of the blastoderm (multipolar immigration). Once these layers have formed, they begin to acquire different structural characters. The embryo is placed in contact with the external environment through the ectoderm, while the endoderm will perform very basic nutritional functions. When two layers have formed in less evolved animals (jellyfish), morphogenesis, which has formed the gastrula, has completed most of the adult form. In more advanced animals, adult structures are more complex, so further cell divisions and growth are needed, leading to the formation of the mesoderm.
Distinction by Number of Layers
Diploblasty
Some animals, such as poriferans and coelenterates, maintain the diploblastic stage, meaning they have only two blastoderm layers. For example, polyps have two layers and can look like an inverted gastrula, with the mesoglea being equivalent to the blastocoel and the inner cavity in contact with the outside being equivalent to the archenteron. However, their gastroporo is not equivalent to the blastopore, as they have different embryonic origins. These animals are representatives of a very simple level of organization that does not have organs, only tissues.
Triploblasty
To form more complex bodies, a third blastoderm layer, the mesoderm, has to develop. However, this does not increase the volume significantly. In the triploblastic gastrula, endoderm cells invaginate to form pockets that expand to create a third blastoderm layer, the mesoderm, between the endoderm and ectoderm. The mesoderm has two layers: the somatopleure, close to the ectoderm, and the splanchnopleure, close to the endoderm.
The mesoderm, together with the mediastinum (which will lead to a cavity or coelom), delimits the mesentery. Animals with three blastoderm layers are called triploblastic and can be acoelomate, pseudocoelomate, or eucoelomate. Mesoderm formation by the process described above is called enterocoelous, but it is not the only mechanism for mesoderm formation.
General Features
Gastrulation is a set of movements of parts of the early embryo (morphogenetic movements) intended to outline the organs of the embryo. Thus, at the end of gastrulation, there is an embryo with three fully differentiated cell layers. The blastomeres move, giving rise to ectodermal organs (on the surface), mesodermal organs (in the middle), and endodermal organs (inside).
Seven Key Features
- Rearrangement of cells by morphogenetic movements.
- Changes in cell shape.
- Little or no growth (the cells are segmented but do not grow much).
- Modification of metabolism, increasing oxidation.
- Increased activity of the nucleus to control the processes that occur in embryonic cells.
- Begins the synthesis of new proteins.
- Cell differentiation begins.
Gastrulation Disorders
- Situs inversus
- Situs ambiguus
- Holoprosencephaly\n
- Caudal dysgenesis (sirenomelia)
- Sacrococcygeal teratoma: Remnants of the primitive streak – Tumor
As derived from stem cells, these tumors contain different types of tissue (hair, nails, bone, etc.). It is the most common tumor in infants (1:35,000 live births). 80% of cases are female.
Larval Development in Fish
During this period, fish larvae develop mainly food and respiratory organs. The yolk sac provides the material necessary for their growth and development. The size of the yolk sac decreases slowly until complete resorption, shortly after the larva begins to eat externally. The duration of this period depends, therefore, on the initial size of the yolk sac, which varies from species to species, and the larval development rate, which varies mainly with the water temperature. For each species, there is an optimal thermal range, similar to that defined for the incubation of eggs. The duration of the larval rearing period is defined in terms of degree days (gd), very similar to the incubation period. This corresponds roughly to three to four days for almost all warm water fish, although it is somewhat longer for colder water fish.