Gastrulation

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.

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).

The major distinctions between deuterostomes and protostomes are found in embryonic development:

• 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
  • Protostomes have what is known as spiral cleavage which is determinate, meaning that the fate of the cells is determined as they are formed.
  • Deuterostomes have what is known as radial cleavage that is indeterminate.

Sea urchins have been important model organisms in developmental biology since the 19th century.[11] Their gastrulation is often considered the archetype for invertebrate deuterostomes.[12] 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.[13]

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

During gastrulation, the cells are differentiated into the ectoderm or mesendoderm, which then separates into the mesoderm and endoderm.[20] 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.[29] 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.[20] 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.[20] RA signaling also has multiple uses in organ formation of the pharyngeal arches, the foregut, and hindgut.[20]

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[30][31][32] and 3D cell (Embryonic organoids) culture techniques[33][34][35][36] 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[34][35] 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[30] (e.g. transient brachyury up regulation and the cellular changes associated with an epithelial to mesenchymal transition[30]), 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.[31][32] 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).[33][34][35][37]

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.[38] 14 days after fertilization the primitive streak forms. The formation of the primitive streak has been known to some countries as “human individuality."[39] 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.[40] 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.

• Blastocyst
• Deuterostome
• Fate mapping
• Primitive knot
• Invagination
• Neurulation
• Protostome
• Vegetal rotation

• Baron, Margaret H. (2001). "Embryonic Induction of Mammalian Hematopoiesis and Vasculogenesis". In Zon, Leonard I. (ed.). Hematopoiesis: a developmental approach. Oxford University Press. ISBN 978-0-19-512450-7.
• Cullen, K.E. (2009). "embryology and early animal development". Encyclopedia of life science, Volume 2. Infobase. ISBN 978-0-8160-7008-4.
• Forgács, G. & Newman, Stuart A. (2005). "Cleavage and blastula formation". Biological physics of the developing embryo. Cambridge University Press. Bibcode:2005bpde.book.....F. ISBN 978-0-521-78337-8.{{cite book}}: CS1 maint: uses authors parameter (link)
• Forgács, G. & Newman, Stuart A. (2005). "Epithelial morphogenesis: gastrulation and neurulation". Biological physics of the developing embryo. Cambridge University Press. Bibcode:2005bpde.book.....F. ISBN 978-0-521-78337-8.{{cite book}}: CS1 maint: uses authors parameter (link)
• Hart, Nathan H. & Fluck, Richard A. (1995). "Epiboly and Gastrulation". In Capco, David (ed.). Cytoskeletal mechanisms during animal development. Academic Press. ISBN 978-0-12-153131-7.{{cite book}}: CS1 maint: uses authors parameter (link)
• Knust, Elizabeth (1999). "Gastrulation movements". In Birchmeier, Walter; Birchmeier, Carmen (eds.). Epithelial Morphogenesis in Development and Disease. CRC Press. pp. 152–153. ISBN 978-90-5702-419-1.
• Kunz, Yvette W. (2004). "Gastrulation". Developmental biology of Teleost fishes. Springer. ISBN 978-1-4020-2996-7.
• Nation, James L., ed. (2009). "Gastrulation". Insect physiology and biochemistry. CRC Press. ISBN 978-0-8493-1181-9.
• Ross, Lawrence M.; Lamperti, Edward D., eds. (2006). "Human Ontogeny: Gastrulation, Neurulation, and Somite Formation". Atlas of anatomy: general anatomy and musculoskeletal system. Thieme. ISBN 978-3-13-142081-7.
• Sanes, Dan H. et al. (2006). "Early embryology of metazoans". Development of the nervous system (2nd ed.). Academic Press. pp. 1–2. ISBN 978-0-12-618621-5.{{cite book}}: CS1 maint: uses authors parameter (link)
• Stanger, Ben Z. & Melton, Douglas A. (2004). "Development of Endodermal Derivatives in the Lungs, Liver, Pancreas, and Gut". In Epstein, Charles J.; et al. (eds.). Inborn errors of development: the molecular basis of clinical disorders of morphogenesis. Oxford University Press. ISBN 978-0-19-514502-1.{{cite book}}: CS1 maint: uses authors parameter (link)

• Gastrulation animations Archived 2015-10-20 at the Wayback Machine
• Gastrulation illustrations and movies from Gastrulation: From Cells To Embryo edited by Claudio Stern
• A video of frog gastrulation