Editing Gastrulation (section)

== 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]]<ref name="Turner-2014">{{Cite journal|last1=Turner|first1=David A.|last2=Rué|first2=Pau|last3=Mackenzie|first3=Jonathan P.|last4=Davies|first4=Eleanor|last5=Martinez Arias|first5=Alfonso|date=2014-01-01|title=Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells|journal=BMC Biology|volume=12|page=63|doi=10.1186/s12915-014-0063-7|issn=1741-7007|pmc=4171571|pmid=25115237 |doi-access=free }}</ref><ref name="Warmflash-2014">{{Cite journal|last1=Warmflash|first1=Aryeh|last2=Sorre|first2=Benoit|last3=Etoc|first3=Fred|last4=Siggia|first4=Eric D|last5=Brivanlou|first5=Ali H|title=A method to recapitulate early embryonic spatial patterning in human embryonic stem cells|journal=Nature Methods|volume=11|issue=8|pages=847–854|doi=10.1038/nmeth.3016|pmc=4341966|pmid=24973948|year=2014}}</ref><ref name="Etoc-2016">{{Cite journal|last1=Etoc|first1=Fred|last2=Metzger|first2=Jakob|last3=Ruzo|first3=Albert|last4=Kirst|first4=Christoph|last5=Yoney|first5=Anna|last6=Ozair|first6=M. Zeeshan|last7=Brivanlou|first7=Ali H.|last8=Siggia|first8=Eric D.|title=A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization|journal=Developmental Cell|volume=39|issue=3|pages=302–315|doi=10.1016/j.devcel.2016.09.016|pmid=27746044|pmc=5113147|year=2016}}</ref> and 3D cell ([[Gastruloid|Embryonic organoids]]) culture techniques<ref name="Brink-2014">{{Cite journal|last1=Brink|first1=Susanne C. van den|last2=Baillie-Johnson|first2=Peter|last3=Balayo|first3=Tina|last4=Hadjantonakis|first4=Anna-Katerina|last5=Nowotschin|first5=Sonja|last6=Turner|first6=David A.|last7=Arias|first7=Alfonso Martinez|date=2014-11-15|title=Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells|journal=Development|language=en|volume=141|issue=22|pages=4231–4242|doi=10.1242/dev.113001|issn=0950-1991|pmc=4302915|pmid=25371360}}</ref><ref name="Turner-2016">{{Cite bioRxiv|last1=Turner|first1=David Andrew|last2=Glodowski|first2=Cherise R.|last3=Luz|first3=Alonso-Crisostomo|last4=Baillie-Johnson|first4=Peter|last5=Hayward|first5=Penny C.|last6=Collignon|first6=Jérôme|last7=Gustavsen|first7=Carsten|last8=Serup|first8=Palle|last9=Schröter|first9=Christian|date=2016-05-13|title=Interactions between Nodal and Wnt signalling Drive Robust Symmetry Breaking and Axial Organisation in Gastruloids (Embryonic Organoids)|biorxiv=10.1101/051722}}</ref><ref name="Turner-2017">{{Cite bioRxiv|last1=Turner|first1=David|last2=Alonso-Crisostomo|first2=Luz|last3=Girgin|first3=Mehmet|last4=Baillie-Johnson|first4=Peter|last5=Glodowski|first5=Cherise R.|last6=Hayward|first6=Penelope C.|last7=Collignon|first7=Jérôme|last8=Gustavsen|first8=Carsten|last9=Serup|first9=Palle|date=2017-01-31|title=Gastruloids develop the three body axes in the absence of extraembryonic tissues and spatially localised signalling|biorxiv=10.1101/104539}}</ref><ref>{{Cite journal|last1=Beccari|first1=Leonardo|last2=Moris|first2=Naomi|last3=Girgin|first3=Mehmet|last4=Turner|first4=David A.|last5=Baillie-Johnson|first5=Peter|last6=Cossy|first6=Anne-Catherine|last7=Lutolf|first7=Matthias P.|last8=Duboule|first8=Denis|last9=Arias|first9=Alfonso Martinez|date=October 2018|title=Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids|journal=Nature|language=En|volume=562|issue=7726|pages=272–276|doi=10.1038/s41586-018-0578-0|pmid=30283134|issn=0028-0836|bibcode=2018Natur.562..272B|s2cid=52915553|url=https://www.repository.cam.ac.uk/handle/1810/285960}}</ref> using [[embryonic stem cell]]s (ESCs) or [[induced pluripotent stem cell]]s (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<ref name="Turner-2016" /><ref name="Turner-2017" /> 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<ref name="Turner-2014" /> (e.g. transient [[brachyury]] up regulation and the cellular changes associated with an [[Epithelial–mesenchymal transition|epithelial to mesenchymal transition]]<ref name="Turner-2014" />), 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 layer]]s in the human embryo.<ref name="Warmflash-2014" /><ref name="Etoc-2016" /> 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).<ref name="Brink-2014" /><ref name="Turner-2016" /><ref name="Turner-2017" /><ref>{{Cite journal|last1=Turner|first1=David A.|last2=Girgin|first2=Mehmet|last3=Alonso-Crisostomo|first3=Luz|last4=Trivedi|first4=Vikas|last5=Baillie-Johnson|first5=Peter|last6=Glodowski|first6=Cherise R.|last7=Hayward|first7=Penelope C.|last8=Collignon|first8=Jérôme|last9=Gustavsen|first9=Carsten|date=2017-11-01|title=Anteroposterior polarity and elongation in the absence of extra-embryonic tissues and of spatially localised signalling in gastruloids: mammalian embryonic organoids|journal=Development|language=en|volume=144|issue=21|pages=3894–3906|doi=10.1242/dev.150391|issn=0950-1991|pmid=28951435|pmc=5702072}}</ref>

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.<ref>{{Cite web |title=In vitro fertilization (IVF) - Mayo Clinic |url=https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716 |access-date=2022-04-11 |website=www.mayoclinic.org}}</ref> 14 days after fertilization the primitive streak forms. The formation of the primitive streak has been known to some countries as "human individuality".<ref>{{Cite journal |last=Asplund |first=Kjell |date=2020 |title=Use of in vitro fertilization—ethical issues |url=https://ujms.net/index.php/ujms/article/view/5673 |journal=Upsala Journal of Medical Sciences |language=en |volume=125 |issue=2 |pages=192–199 |doi=10.1080/03009734.2019.1684405 |pmid=31686575 |pmc=7721055 |s2cid=207896932 |issn=2000-1967}}</ref> 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.<ref>{{Cite journal |last=Davis |first=Caitlin |date=2019-03-01 |title=The Boundaries of Embryo Research: Extending the Fourteen-Day Rule |journal=Journal of Bioethical Inquiry |language=en |volume=16 |issue=1 |pages=133–140 |doi=10.1007/s11673-018-09895-w |pmid=30635823 |s2cid=58643344 |issn=1872-4353}}</ref> 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.