Gastrulation

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Gastrulation
Blastula.png
Gastrulation occurs when a 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
MeSH D054262
Anatomical terminology

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. [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]

Contents

Gastrula layers

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

In triploblastic organisms, the gastrula is trilaminar (three-layered). These three germ layers are the ectoderm (outer layer), mesoderm (middle layer), and endoderm (inner layer). [3] [4] In diploblastic 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. [5] Sponges 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. [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 γαστήρgastḗr ("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]

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. Model organisms 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

Protovsdeuterostomes.svg

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]

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. [14]

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. [15]

Amphibians

The frog genus Xenopus has been used as a model organism for the study of gastrulation. [16]

Symmetry breaking

The sperm contributes one of the two 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 organizer. Thus, the area on the vegetal side opposite the sperm entry point will become the organizer. [17] Hilde Mangold, working in the lab of Hans Spemann, demonstrated that this special "organizer" of the embryo is necessary and sufficient to induce gastrulation. [18] [19] [20]

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

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. [17]

Cell signaling

In the frog, Xenopus, one of the signals is retinoic acid (RA). [21] 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. [21]

Amniotes

Overview

In 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 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 asymmetric; (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. [7]

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, 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. [7]

Epithelial-mesenchymal transition - loss of cell adhesion leads to constriction and extrusion of newly formed mesenchymal cell. Epithelial-mesenchymal transition scheme.png
Epithelial–mesenchymal transition – loss of cell adhesion leads to constriction and extrusion of newly formed mesenchymal cell.

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. [22] Formation of the primitive streak is reliant upon nodal signaling [7] in the Koller's sickle within the cells contributing to the primitive streak and BMP4 signaling from the extraembryonic tissue. [22] [23] Furthermore, Cer1 and Lefty1 restrict the primitive streak to the appropriate location by antagonizing nodal signaling. [24] 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 bilateral symmetry, determine the site of gastrulation and initiate germ layer formation. [25] To form the streak, reptiles, birds and mammals arrange mesenchymal cells along the prospective midline, establishing the first embryonic axis, as well as the place where cells will ingress and migrate during the process of gastrulation and germ layer formation. [26] The primitive streak extends through this midline and creates the antero-posterior body axis, [27] becoming the first symmetry-breaking event in the embryo, and marks the beginning of gastrulation. [28] This process involves the ingression of mesoderm and endoderm progenitors and their migration to their ultimate position, [27] [29] where they will differentiate into the three germ layers. [26] The localization of the cell adhesion and signaling molecule 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 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–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. [24]

Cell signaling driving gastrulation

During gastrulation, the cells are differentiated into the ectoderm or mesendoderm, which then separates into the mesoderm and endoderm. [21] 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 β-catenin plays a key role in nodal signaling and endoderm formation. [30] 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. [21] 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. [21] RA signaling also has multiple uses in organ formation of the pharyngeal arches, the foregut, and hindgut. [21]

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 [31] [32] [33] and 3D cell (Embryonic organoids) culture techniques [34] [35] [36] [37] 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 [35] [36] 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 [31] (e.g. transient brachyury up regulation and the cellular changes associated with an epithelial to mesenchymal transition [31] ), 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. [32] [33] 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). [34] [35] [36] [38]

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. [39] 14 days after fertilization the primitive streak forms. The formation of the primitive streak has been known to some countries as "human individuality". [40] 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. [41] 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

Related Research Articles

<span class="mw-page-title-main">Mesoderm</span> Middle germ layer of embryonic development

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.

<span class="mw-page-title-main">Blastulation</span> Sphere of cells formed during early embryonic development in animals

Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development, the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.

<span class="mw-page-title-main">Blastocoel</span> Fluid-filled or yolk-filled cavity that forms in the blastula

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 mammals the blastula is called the blastocyst, which consists of an outer epithelium, the trophectoderm, enveloping the inner cell mass and the blastocoel.

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 produce two or three primary germ layers. Some animals, like cnidarians, produce two germ layers making them diploblastic. Other animals such as bilaterians produce a third layer between these two layers, making them triploblastic. Germ layers eventually give rise to all of an animal's tissues and organs through the process of organogenesis.

<span class="mw-page-title-main">Animal embryonic development</span> Process by which the embryo forms and develops

In developmental biology, animal embryonic development, also known as animal embryogenesis, is the developmental stage of an animal embryo. Embryonic development starts with the fertilization of an egg cell (ovum) by a sperm cell (spermatozoon). Once fertilized, the ovum becomes a single diploid cell known as a zygote. The zygote undergoes mitotic divisions with no significant growth and cellular differentiation, leading to development of a multicellular embryo after passing through an organizational checkpoint during mid-embryogenesis. In mammals, the term refers chiefly to the early stages of prenatal development, whereas the terms fetus and fetal development describe later stages.

<span class="mw-page-title-main">Neurula</span> Embryo at the early stage of development in which neurulation occurs

A neurula is a vertebrate embryo at the early stage of development in which neurulation occurs. The neurula stage is preceded by the gastrula stage; consequentially, neurulation is preceded by gastrulation. Neurulation marks the beginning of the process of organogenesis.

The primitive node is the organizer for gastrulation in most amniote embryos. In birds, it is known as Hensen's node, and in amphibians, it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in amphibians, or by the posterior marginal zone in amniotes including birds.

<span class="mw-page-title-main">Primitive streak</span> Structure in early amniote embryogenesis

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 broad end towards the anterior, and the narrower region projected to the posterior. The primitive streak forms a longitudinal midline structure in the narrower posterior (caudal) region of the developing embryo on its dorsal side. At first formation, the primitive streak extends for half the length of the embryo. In the human embryo, this appears by stage 6, about 17 days.

<span class="mw-page-title-main">Epiblast</span> Embryonic inner cell mass tissue that forms the embryo itself, through the three germ layers

In amniote embryonic development, the epiblast 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 is the hypoblast. It drives the embryo proper through its differentiation into the three primary germ layers, ectoderm, mesoderm and endoderm, during gastrulation. The amniotic ectoderm and extraembryonic mesoderm also originate from the epiblast.

<span class="mw-page-title-main">Mesenchyme</span> Type of animal embryonic connective tissue

Mesenchyme is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every organ in the developing embryo.

<span class="mw-page-title-main">Bilaminar embryonic disc</span>

The bilaminar embryonic disc, bilaminar blastoderm or embryonic disc is the distinct two-layered structure of cells formed in an embryo. In the development of the human embryo this takes place by day eight. It is formed when the inner cell mass, also known as the embryoblast, forms a bilaminar disc of two layers, an upper layer called the epiblast and a lower layer called the hypoblast, which will eventually form into fetus. These two layers of cells are stretched between two fluid-filled cavities at either end: the primitive yolk sac and the amniotic sac.

In the field of developmental biology, regional differentiation is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.

<span class="mw-page-title-main">Fish development</span>

The development of fishes is unique in some specific aspects compared to the development of other animals.

<span class="mw-page-title-main">Human embryonic development</span> Development and formation of the human embryo

Human embryonic development or human embryogenesis is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development. In biological terms, the development of the human body entails growth from a one-celled zygote to an adult human being. Fertilization occurs when the sperm cell successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then combine to form the single cell zygote and the germinal stage of development commences. Human embryonic development covers the first eight weeks of development, which have 23 stages, called Carnegie stages. At the beginning of the ninth week, the embryo is termed a fetus. In comparison to the embryo, the fetus has more recognizable external features and a more complete set of developing organs.

<span class="mw-page-title-main">Hypoblast</span> Embryonic inner cell mass tissue that forms the yolk sac and, later, chorion

In amniote embryology, the hypoblast is one of two distinct layers arising from the inner cell mass in the mammalian blastocyst, or from the blastodisc in reptiles and birds. The hypoblast gives rise to the yolk sac.

<span class="mw-page-title-main">Nodal homolog</span> Mammalian protein found in Homo sapiens

Nodal homolog is a secretory protein that in humans is encoded by the NODAL gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily. Like many other members of this superfamily it is involved in cell differentiation in early embryogenesis, playing a key role in signal transfer from the primitive node, in the anterior primitive streak, to lateral plate mesoderm (LPM).

<span class="mw-page-title-main">Koller's sickle</span>

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 differentiation of various avian body parts. Koller's sickle induces primitive streak and Hensen's node, which are major components of avian gastrulation. Avian gastrulation is a process by which developing cells in an avian embryo move relative to one another in order to form the three germ layers.

<span class="mw-page-title-main">Ingression (biology)</span>

Ingression is one of the many changes in the location or relative position of cells that takes place during the gastrulation stage of embryonic development. It produces an animal's mesenchymal cells at the onset of gastrulation. During the epithelial–mesenchymal transition (EMT), the primary mesenchyme cells (PMCs) detach from the epithelium and become internalized mesenchyme cells that can migrate freely.

Embryogenesis in multicellular organisms can vary across taxonomic class or species. Organisms independent of aquatic habitats exhibit unique features during their embryonic development. Amphibians are notable as remnants of the first vertebrates capable of surviving in both aquatic and terrestrial environments. The embryonic development of tailless amphibians is presented below using the African clawed frog and the northern leopard frog as examples.

This glossary of developmental biology is a list of definitions of terms and concepts commonly used in the study of developmental biology and related disciplines in biology, including embryology and reproductive biology, primarily as they pertain to vertebrate animals and particularly to humans and other mammals. The developmental biology of invertebrates, plants, fungi, and other organisms is treated in other articles; e.g terms relating to the reproduction and development of insects are listed in Glossary of entomology, and those relating to plants are listed in Glossary of botany.

References

Notes

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  38. ↑ Turner, David A.; Girgin, Mehmet; Alonso-Crisostomo, Luz; Trivedi, Vikas; Baillie-Johnson, Peter; Glodowski, Cherise R.; Hayward, Penelope C.; Collignon, Jérôme; Gustavsen, Carsten (2017-11-01). "Anteroposterior polarity and elongation in the absence of extra-embryonic tissues and of spatially localised signalling in gastruloids: mammalian embryonic organoids". Development. 144 (21): 3894–3906. doi:10.1242/dev.150391. ISSN   0950-1991. PMC   5702072 . PMID   28951435.
  39. ↑ "In vitro fertilization (IVF) - Mayo Clinic". www.mayoclinic.org. Retrieved 2022-04-11.
  40. ↑ Asplund, Kjell (2020). "Use of in vitro fertilization—ethical issues". Upsala Journal of Medical Sciences. 125 (2): 192–199. doi:10.1080/03009734.2019.1684405. ISSN   2000-1967. PMC   7721055 . PMID   31686575. S2CID   207896932.
  41. ↑ Davis, Caitlin (2019-03-01). "The Boundaries of Embryo Research: Extending the Fourteen-Day Rule". Journal of Bioethical Inquiry. 16 (1): 133–140. doi:10.1007/s11673-018-09895-w. ISSN   1872-4353. PMID   30635823. S2CID   58643344.

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