View source for Biology:Human embryonic development

{{Short description|Development and formation of the human embryo}}
[[File:HumanEmbryogenesis.svg|thumb|400px|The initial stages of human embryonic development ([[Biology:Embryogenesis|embryogenesis]])]]
{{Human growth and development}}
'''Human embryonic development''' or '''human embryogenesis''' is the development and formation of the human [[Biology:Embryo|embryo]]. It is characterised by the processes of [[Biology:Cell division|cell division]] and [[Biology:Cellular differentiation|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 [[Biology:Zygote|zygote]] to an adult human being. Fertilization occurs when the [[Biology:Spermatozoon|sperm cell]] successfully enters and [[Biology:Cell fusion|fuses]] with an [[Biology:Egg cell|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. Embryonic development in the human, covers the first eight weeks of development; at the beginning of the ninth week the embryo is termed a [[Biology:Fetus|fetus]].
The eight weeks has 23 stages.

'''Human embryology''' is the study of this development during the first eight weeks after fertilization. The normal period of gestation (pregnancy) is about nine months or 40 weeks.

The germinal stage refers to the time from fertilization through the development of the early embryo until [[Biology:Implantation (embryology)|implantation]] is completed in the [[Biology:Uterus|uterus]]. The germinal stage takes around 10 days.<ref>{{cite web|title=germinal stage|url=http://medical-dictionary.thefreedictionary.com/germinal+stage|work=Mosby's Medical Dictionary, 8th edition.|publisher=Elsevier.|access-date=6 October 2013}}</ref> During this stage, the zygote begins to divide, in a process called [[Biology:Cleavage (embryo)|cleavage]]. A [[Biology:Blastocyst|blastocyst]] is then formed and implants in the [[Biology:Uterus|uterus]]. Embryogenesis continues with the next stage of [[Biology:Gastrulation|gastrulation]], when the three germ layers of the embryo form in a process called [[Biology:Histogenesis|histogenesis]], and the processes of neurulation and [[Biology:Organogenesis|organogenesis]] follow.

In comparison to the embryo, the fetus has more recognizable external features and a more complete set of developing organs. The entire process of embryogenesis involves coordinated spatial and temporal changes in [[Biology:Gene expression|gene expression]], [[Biology:Cell growth|cell growth]] and [[Biology:Cellular differentiation|cellular differentiation]]. A nearly identical process occurs in other species, especially among [[Biology:Chordate|chordate]]s.

==Germinal stage==
===Fertilization===
Fertilization takes place when the [[Biology:Spermatozoon|spermatozoon]] has successfully entered the ovum and the two sets of genetic material carried by the [[Biology:Gamete|gamete]]s fuse together, resulting in the zygote (a single diploid cell). This usually takes place in the ampulla of one of the [[Medicine:Fallopian tube|fallopian tube]]s. The zygote contains the combined genetic material carried by both the male and female gametes which consists of the 23 chromosomes from the nucleus of the ovum and the 23 chromosomes from the nucleus of the sperm. The 46 chromosomes undergo changes prior to the mitotic division which leads to the formation of the embryo having two cells.

Successful fertilization is enabled by three processes, which also act as controls to ensure species-specificity. The first is that of [[Physics:Chemotaxis|chemotaxis]] which directs the movement of the sperm towards the ovum.<ref name="Marlow">{{Cite book|last=Marlow|first=Florence L|title=Maternal Effect Genes in Development|date=2020|publisher=Academic Press|isbn=978-0128152218|page=124|url=https://books.google.com/books?id=JX3nDwAAQBAJ&pg=PA124}}</ref> Secondly, an adhesive compatibility between the sperm and the egg occurs. With the sperm adhered to the ovum, the third process of acrosomal reaction takes place; the front part of the spermatozoan head is capped by an [[Medicine:Acrosome|acrosome]] which contains digestive [[Biology:Enzyme|enzyme]]s to break down the [[Biology:Zona pellucida|zona pellucida]] and allow its entry.<ref name="Singh">{{Cite book|last=Singh|first=Vishram|title=Textbook of Clinical Embryology – E-book|date=2013|publisher=Elsevier Health Sciences|isbn=978-8131236208|page=35|url=https://books.google.com/books?id=ABBtAwAAQBAJ&pg=PA35}}</ref> The entry of the sperm causes calcium to be released which blocks entry to other sperm cells.<ref name="Singh"/> A parallel reaction takes place in the ovum called the zona reaction. This sees the release of cortical granules that release enzymes which digest sperm receptor proteins, thus preventing [[Biology:Polyspermy|polyspermy]].<ref name="Standring">{{Cite book|last=Standring|first=Susan|title=Gray's Anatomy E-Book: The Anatomical Basis of Clinical Practice|date=2015|publisher=Elsevier Health Sciences|isbn=978-0702068515|page=163|url=https://books.google.com/books?id=b7FVCgAAQBAJ&pg=PA163}}</ref> The granules also fuse with the plasma membrane and modify the zona pellucida in such a way as to prevent further sperm entry.

=== Cleavage ===
{{Further|Biology:Cleavage (embryo)|Biology:Cleavage furrow}}
[[File:Embryo, 8 cells.jpg|thumb|200px|Eight-cell embryo, at three days]]
The beginning of the [[Biology:Cleavage (embryo)|cleavage]] process is marked when the zygote divides through [[Biology:Mitosis|mitosis]] into two cells. This mitosis continues and the first two cells divide into four cells, then into eight cells and so on. Each division takes from 12 to 24 hours. The zygote is large compared to any other cell and undergoes cleavage without any overall increase in size. This means that with each successive subdivision, the ratio of nuclear to cytoplasmic material increases.<ref name="Cambridge University Press">{{cite book|chapter=Cleavage and blastula formation|title=Biological physics of the developing embryo|publisher=Cambridge University Press|year=2005|isbn=978-0-521-78337-8|page=27|chapter-url=https://books.google.com/books?id=rUyVWQhk7CkC&pg=PA27|author1=Forgács, G. |author2=Newman, Stuart A.}}</ref>

Initially, the dividing cells, called blastomeres ({{transliteration|grc|blastos}} Greek for sprout), are undifferentiated and aggregated into a sphere enclosed within the [[Biology:Zona pellucida|zona pellucida]] of the ovum. When eight [[Biology:Blastomere|blastomere]]s have formed, they start to [[Biology:Cleavage (embryo)#Compaction|compact]].<ref name="Standring2">{{Cite book|last=Standring|first=Susan|title=Gray's Anatomy E-Book: The Anatomical Basis of Clinical Practice|date=2015|publisher=Elsevier Health Sciences|isbn=978-0702068515|page=166|url=https://books.google.com/books?id=b7FVCgAAQBAJ&pg=PA165}}</ref> They begin to develop [[Biology:Gap junction|gap junction]]s, enabling them to develop in an integrated way and co-ordinate their response to physiological signals and environmental cues.<ref name="BrisonSturmey2014">{{cite journal|last1=Brison|first1=D. R.|last2=Sturmey|first2=R. G.|last3=Leese|first3=H. J.|title=Metabolic heterogeneity during preimplantation development: the missing link?|journal=Human Reproduction Update|volume=20|issue=5|year=2014|pages=632–640|issn=1355-4786|doi=10.1093/humupd/dmu018|pmid=24795173|doi-access=free}}</ref>

When the cells number around sixteen, the solid sphere of cells within the zona pellucida is referred to as a [[Biology:Morula|morula]].<ref>{{Cite book|author=Boklage, Charles E.|title=How New Humans Are Made: Cells and Embryos, Twins and Chimeras, Left and Right, Mind/Self/Soul, Sex, and Schizophrenia|publisher=World Scientific|year=2009|isbn=978-981-283-513-0|page=217|url=https://books.google.com/books?id=j7GfgRIgP9YC&pg=PT233}}</ref>

=== Blastulation ===
{{Further |Biology:Polarity in embryogenesis}}
[[File:Diagram of Blastocyst stage.png|thumb|200px|Blastocyst with an inner cell mass and trophoblast]]
Cleavage itself is the first stage in [[Biology:Blastulation|blastulation]], the process of forming the [[Biology:Blastocyst|blastocyst]]. Cells differentiate into an outer layer of cells called the  [[Biology:Trophoblast|trophoblast]], and an [[Biology:Inner cell mass|inner cell mass]]. With further compaction the individual outer blastomeres, the trophoblasts, become indistinguishable. They are still enclosed within the [[Biology:Zona pellucida|zona pellucida]]. This compaction serves to make the structure watertight, containing the fluid that the cells will later secrete. The inner mass of cells differentiate to become embryoblasts and [[Biology:Polarity in embryogenesis|polarise]] at one end. They close together and form [[Biology:Gap junction|gap junction]]s, which facilitate cellular communication. This polarisation leaves a cavity, the [[Biology:Blastocoel|blastocoel]], creating a structure that is now termed the blastocyst. (In animals other than mammals, this is called the [[Biology:Blastula|blastula]]).

The trophoblasts secrete fluid into the blastocoel. The resulting increase in size of the blastocyst causes it to [[Biology:Zona hatching|hatch]] through the zona pellucida, which then disintegrates.<ref name="Cambridge University Press"/> This process is called [[Biology:Zona hatching|zona hatching]] and it takes place on the sixth day of embryo development, immediately before the implantation process. The hatching of the human embryo is supported by proteases secreted by the cells of the blastocyst, which digest proteins of the zona pellucida, giving rise to a hole. Then, due to the rhythmic expansion and contractions of the blastocyst, an increase of the pressure inside the blastocyst itself occurs, the hole expands and finally the blastocyst can emerge from this rigid envelope.

The inner cell mass will give rise to the [[Biology:Pre-embryo|pre-embryo]],<ref name="opentext">{{cite web |title=28.2 Embryonic Development – Anatomy and Physiology |url=https://opentextbc.ca/anatomyandphysiology/chapter/28-2-embryonic-development/ |website=opentextbc.ca}}</ref> the [[Biology:Amnion|amnion]], yolk sac and [[Biology:Allantois|allantois]], while the fetal part of the [[Biology:Placenta|placenta]] will form from the outer trophoblast layer. The embryo plus its [[Biology:Cell membrane|membrane]]s is called the [[Biology:Conceptus|conceptus]], and by this stage the conceptus has reached the [[Biology:Uterus|uterus]]. The zona pellucida ultimately disappears completely, and the now exposed cells of the trophoblast allow the blastocyst to attach itself to the endometrium, where it will [[Biology:Implantation (human embryo)|implant]].
The formation of the [[Biology:Hypoblast|hypoblast]] and [[Biology:Epiblast|epiblast]], which are the two main layers of the bilaminar germ disc, occurs at the beginning of the second week.<ref name=Carlson>{{cite book |last1= Carlson |first1= Bruce M. |title= Human Embryology & Developmental Biology |publisher= Mosby, Inc. |year= 1999 |orig-year=1t. Pub. 1997 |pages= 62–68 |chapter=Chapter 4: Formation of germ layers and initial derivatives |isbn=0-8151-1458-3}}</ref> Both the embryoblast and the trophoblast will turn into two sub-layers.<ref name= Sadler>{{cite book |last1=Sadler |first1=T.W. |last2=Langman |first2=Jan |editor-last= Seigafuse |editor-first=sonya |title=Langman, Embriología médica |publisher=Lippincott Williams & Wilkins, Wolters Kluwer |year= 2012 |orig-year=1st. Pub. 2001 |pages=29–42 |chapter=Chapter 3: Primera semana del desarrollo: de la ovulación a la implantación |isbn=978-84-15419-83-9}}</ref> The inner cells will turn into the hypoblast layer, which will surround the other layer, called the epiblast, and these layers will form the embryonic disc that will develop into the embryo.<ref name=Carlson/><ref name=Sadler/>

The trophoblast will also develop two sub-layers: the [[Biology:Cytotrophoblast|cytotrophoblast]], which is in front of the [[Biology:Syncytiotrophoblast|syncytiotrophoblast]], which in turn lies within the endometrium.<ref name=Carlson/> Next, another layer called the [[Biology:Heuser's membrane|exocoelomic membrane or Heuser's membrane]] will appear and surround the cytotrophoblast, as well as the primitive yolk sac.<ref name=Sadler/> The syncytiotrophoblast will grow and will enter a phase called lacunar stage, in which some vacuoles will appear and be filled by blood in the following days.<ref name=Carlson/><ref name=Sadler/> The development of the yolk sac starts with the [[Medicine:Hypoplasia|hypoblastic]] flat cells that form the exocoelomic membrane, which will coat the inner part of the cytotrophoblast to form the primitive yolk sac. An erosion of the endothelial lining of the maternal capillaries by the syncytiotrophoblastic cells results in the formation of the maternal sinusoids from where the blood will begin to penetrate and flow into and through the trophoblastic lacunae to give rise to the uteroplacental circulation.<ref name=Moore>{{cite book |last1=Moore |first1=Keith L. |last2=Persaud |first2=V.N. |title= The Developing Human, Clinically Oriented Embryology |publisher= W B Saunders Co |year= 2003 |orig-year=1t. Pub. 1996 |pages= 47–51 |chapter=Chapter 3: Formation of the bilaminar embryonic disc: second week |isbn=0-7216-9412-8}}</ref><ref name=Larsen>{{cite book |last1= Larsen |first1= William J. |last2= Sherman |first2= Lawrence S. |last3= Potter |first3= S. Steven |last4= Scott |first4= William J. |title= Human Embryology |publisher= Churchill Livingstone. |year= 2001 |orig-year=1t. Pub. 1998 |pages= 37–45 |chapter=Chapter 2: Bilaminar embryonic disc development and establishment of the uteroplacental circulation | isbn=0-443-06583-7}}</ref> Subsequently, new cells derived from yolk sac will be established between trophoblast and exocoelomic membrane and will give rise to extra-embryonic [[Biology:Mesoderm|mesoderm]], which will form the [[Biology:Chorion|chorionic cavity]].<ref name=Sadler/>

At the end of the second week of development, some cells of the trophoblast penetrate and form rounded columns into the syncytiotrophoblast. These columns are known as [[Biology:Chorionic villi|primary villi]]. At the same time, other migrating cells form into the exocoelomic cavity a new cavity named the secondary or definitive yolk sac, smaller than the primitive yolk sac.<ref name=Sadler/><ref name=Moore/>

=== Implantation ===
{{Main|Biology:Implantation (embryology)}}
[[File:Gray36.png|thumb|200px|Trophoblast differentiation]]
After ovulation, the endometrial lining becomes transformed into a secretory lining in preparation of accepting the embryo. It becomes thickened, with its secretory glands becoming elongated, and is increasingly [[Medicine:Vascular|vascular]]. This lining of the uterine cavity (or womb) is now known as the [[Medicine:Decidua|decidua]], and it produces a great number of large [[Biology:Decidual cells|decidual cells]] in its increased interglandular tissue. The blastomeres in the blastocyst are arranged into an outer layer called the [[Biology:Trophoblast|trophoblast]]. The trophoblast then differentiates into an inner layer, the [[Biology:Cytotrophoblast|cytotrophoblast]], and an outer layer, the [[Biology:Syncytiotrophoblast|syncytiotrophoblast]]. The cytotrophoblast contains cuboidal epithelial [[Biology:Cell|cells]] and is the source of [[Biology:Cell division|dividing cells]], and the syncytiotrophoblast is a [[Biology:Syncytium|syncytial]] layer without cell boundaries.

The syncytiotrophoblast implants the blastocyst in the decidual [[Biology:Epithelium|epithelium]] by projections of [[Biology:Chorionic villi|chorionic villi]], forming the embryonic part of the placenta. The placenta develops once the blastocyst is implanted, connecting the embryo to the uterine wall. The decidua here is termed the decidua basalis; it lies between the blastocyst and the myometrium and forms the maternal part of the [[Biology:Placenta|placenta]]. The implantation is assisted by hydrolytic [[Biology:Enzyme|enzyme]]s that erode the [[Biology:Epithelium|epithelium]]. The [[Biology:Syncytiotrophoblast|syncytiotrophoblast]] also produces [[Chemistry:Human chorionic gonadotropin|human chorionic gonadotropin]], a [[Biology:Hormone|hormone]] that stimulates the release of [[Chemistry:Progesterone|progesterone]] from the [[Biology:Corpus luteum|corpus luteum]]. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can oxygenate and sustain the developing embryo. The uterus liberates sugar from stored [[Biology:Glycogen|glycogen]] from its cells to nourish the [[Biology:Embryo|embryo]].<ref>{{cite book |last=Campbell |first=Neil A. |author2=Brad Williamson |author3=Robin J. Heyden |title=Biology: Exploring Life |publisher=Pearson Prentice Hall |year=2006 |location=Boston |url=http://www.phschool.com/el_marketing.html |isbn=0-13-250882-6 }}</ref> The villi begin to branch and contain blood vessels of the embryo. Other villi, called terminal or free villi, exchange nutrients. The embryo is joined to the trophoblastic shell by a narrow connecting stalk that develops into the umbilical cord to attach the placenta to the embryo.<ref name=Sadler/><ref name=Smith/>
Arteries in the decidua are remodelled to increase the maternal blood flow into the intervillous spaces of the placenta, allowing [[Biology:Respiration (physiology)|gas exchange]] and the transfer of nutrients to the embryo. Waste products from the embryo will diffuse across the placenta.

As the syncytiotrophoblast starts to penetrate the uterine wall, the inner cell mass (embryoblast) also develops. The inner cell mass is the source of embryonic stem cells, which are pluripotent and can develop into any one of the three germ layer cells, and which have the potency to give rise to all the tissues and organs.
===Embryonic disc===
The embryoblast forms an [[Biology:Bilaminar embryonic disc|embryonic disc]] of two layers, the upper layer is called the [[Biology:Epiblast|epiblast]] and the lower layer, the [[Biology:Hypoblast|hypoblast]]. The disc is stretched between what will become the amniotic cavity and the yolk sac. The epiblast is adjacent to the trophoblast and made of columnar cells; the hypoblast is closest to the blastocyst cavity and made of cuboidal cells. The epiblast migrates away from the trophoblast downwards, forming the amniotic cavity, the lining of which is formed from amnioblasts developed from the epiblast. The hypoblast is pushed down and forms the yolk sac (exocoelomic cavity) lining. Some hypoblast cells migrate along the inner cytotrophoblast lining of the blastocoel, secreting an [[Biology:Extracellular matrix|extracellular matrix]] along the way. These hypoblast cells and extracellular matrix are called [[Biology:Heuser's membrane|Heuser's membrane]] (or the exocoelomic membrane), and they cover the blastocoel to form the yolk sac (or exocoelomic cavity). Cells of the hypoblast migrate along the outer edges of this reticulum and form the extraembryonic mesoderm; this disrupts the extraembryonic reticulum. Soon pockets form in the reticulum, which ultimately coalesce to form the [[Biology:Gestational sac|chorionic cavity]] (extraembryonic coelom).

==Gastrulation==
{{Main|Biology:Gastrulation}}
[[File:Germ layers.jpg|thumb|650px|[[Biology:Histogenesis|Histogenesis]] of the three germ layers]]
[[File:Ultrasound of embryo at 5 weeks, colored.png|thumb|200px|Artificially colored – [[Biology:Gestational sac|gestational sac]], yolk sac and embryo (measuring 3&nbsp;mm at five weeks)]]
[[File:2910 The Placenta-02.jpg|420px|thumb|Embryo attached to placenta in amniotic cavity]]

The [[Biology:Primitive streak|primitive streak]], a linear collection of cells formed by the migrating epiblast, appears, and this marks the beginning of [[Biology:Gastrulation|gastrulation]], which takes place around the seventeenth day (week 3) after fertilization. The process of gastrulation reorganises the two-layer embryo into a three-layer embryo, and also gives the embryo its specific head-to-tail, and front-to-back orientation, by way of the primitive streak which establishes bilateral symmetry. A [[Biology:Primitive node|primitive node]] (or primitive knot) forms in front of the primitive streak which is the organiser of neurulation. A [[Biology:Primitive pit|primitive pit]] forms as a depression in the centre of the primitive node which connects to the notochord which lies directly underneath. The node has arisen from epiblasts of the amniotic cavity floor, and it is this node that induces the formation of the neural plate which serves as the basis for the nervous system.

The neural plate will form opposite the primitive streak from ectodermal tissue which thickens and flattens into the neural plate. The epiblast in that region moves down into the streak at the location of the primitive pit where the process called [[Biology:Ingression|ingression]], which leads to the formation of the mesoderm takes place. This ingression sees the cells from the epiblast move into the primitive streak in an epithelial-mesenchymal transition; epithelial cells become mesenchymal stem cells, multipotent stromal cells that can [[Biology:Cellular differentiation|differentiate]] into various cell types. The hypoblast is pushed out of the way and goes on to form the [[Biology:Amnion|amnion]]. The epiblast keeps moving and forms a second layer, the mesoderm. The epiblast has now differentiated into the three [[Biology:Germ layer|germ layer]]s of the embryo, so that the bilaminar disc is now a trilaminar disc, the gastrula.

The three germ layers are the [[Biology:Ectoderm|ectoderm]], [[Biology:Mesoderm|mesoderm]] and [[Biology:Endoderm|endoderm]], and are formed as three overlapping flat discs. It is from these three layers that all the structures and organs of the body will be derived through the processes of [[Biology:Somitogenesis|somitogenesis]], [[Biology:Histogenesis|histogenesis]] and [[Biology:Organogenesis|organogenesis]].<ref>{{Cite book |last=Schünke |first=Michael |url=https://books.google.com/books?id=NK9TgTaGt6UC&pg=PA6 |title=Thieme Atlas of Anatomy: General Anatomy and Musculoskeletal System |last2=Ross |first2=Lawrence M. |last3=Schulte |first3=Erik |last4=Schumacher |first4=Udo |last5=Lamperti |first5=Edward D. |date=2006 |publisher=Thieme |isbn=978-3-13-142081-7 |language=en}}</ref> The embryonic endoderm is formed by [[Philosophy:Invagination|invagination]] of epiblastic cells that migrate to the hypoblast, while the mesoderm is formed by the cells that develop between the epiblast and endoderm. In general, all germ layers will derive from the epiblast.<ref name=Sadler/><ref name=Smith>{{cite book |last1= Smith Agreda |first1= Víctor |last2= Ferrés Torres |first2= Elvira |last3= Montesinos Castro-Girona |first3= Manuel |title= Manual de embriología y anatomía general |publisher= Universitat de València |year= 1992 |pages= 72–85 |chapter=Chapter 5: Organización del desarrollo: Fase de germinación |isbn=84-370-1006-3}}</ref> The upper layer of ectoderm will give rise to the outermost layer of skin, central and peripheral [[Biology:Nervous system|nervous system]]s, eyes, inner ear, and many connective tissues.<ref name="D">{{cite web|url=http://www.mayoclinic.com/health/prenatal-care/PR00112/NSECTIONGROUP=2 |title=Pregnancy week by week|access-date=28 July 2010}}</ref> The middle layer of mesoderm will give rise to the heart and the beginning of the [[Biology:Circulatory system|circulatory system]] as well as the [[Biology:Bone|bone]]s, muscles and kidneys. The inner layer of endoderm will serve as the starting point for the development of the lungs, [[Chemistry:Intestine|intestine]], [[Biology:Thyroid|thyroid]], pancreas and [[Biology:Urinary bladder|bladder]].

Following ingression, a [[Biology:Gastrulation#Overview|blastopore]] develops where the cells have ingressed, in one side of the embryo and it deepens to become the [[Biology:Archenteron|archenteron]], the first formative stage of the gut. As in all [[Biology:Deuterostome|deuterostome]]s, the blastopore becomes the [[Biology:Anus|anus]] whilst the gut tunnels through the embryo to the other side where the opening becomes the mouth. With a functioning digestive tube, gastrulation is now completed and the next stage of neurulation can begin.

==Neurulation==
[[File:Neural crest.svg|220px|thumb|left|Neural plate]]
[[File:Embryonic Development CNS.png|thumb|280px|Neural tube development]]
Following gastrulation, the ectoderm gives rise to epithelial and [[Biology:Nervous tissue|neural tissue]], and the gastrula is now referred to as the neurula. The neural plate that has formed as a thickened plate from the ectoderm, continues to broaden and its ends start to fold upwards as neural folds. Neurulation refers to this folding process whereby the neural plate is transformed into the [[Biology:Neural tube|neural tube]], and this takes place during the fourth week. They fold, along a shallow neural groove which has formed as a dividing median line in the neural plate. This deepens as the folds continue to gain height, when they will meet and close together at the [[Biology:Neural crest|neural crest]]. The cells that migrate through the most cranial part of the primitive line form the [[Biology:Paraxial mesoderm|paraxial mesoderm]], which will give rise to the somitomeres that in the process of [[Biology:Somitogenesis|somitogenesis]] will differentiate into [[Biology:Somite|somite]]s that will form the sclerotomes, the [[Biology:Somite|syndetome]]s,<ref name="pmid12705871">{{cite journal |vauthors=Brent AE, Schweitzer R, Tabin CJ |title=A somitic compartment of tendon progenitors |journal=Cell |volume=113 |issue=2 |pages=235–48 |date=April 2003 |pmid=12705871 |doi= 10.1016/S0092-8674(03)00268-X|s2cid=16291509 |doi-access=free }}</ref> the [[Biology:Myotome|myotome]]s and the [[Biology:Somite|dermatome]]s to form [[Biology:Cartilage|cartilage]] and [[Biology:Bone|bone]], [[Biology:Tendon|tendon]]s, [[Biology:Dermis|dermis]] (skin), and [[Biology:Muscle|muscle]]. The intermediate mesoderm gives rise to the urogenital tract and consists of cells that migrate from the middle region of the primitive line. Other cells migrate through the caudal part of the primitive line and form the lateral mesoderm, and those cells migrating by the most caudal part contribute to the extraembryonic mesoderm.<ref name=Sadler/><ref name=Smith/>

The embryonic disc begins flat and round, but eventually elongates to have a wider cephalic part and narrow-shaped caudal end.<ref name=Carlson/> At the beginning, the primitive line extends in [[Biology:Cephalic|cephalic]] direction and 18 days after fertilization returns caudally until it disappears. In the cephalic portion, the germ layer shows specific differentiation at the beginning of the fourth week, while in the caudal portion it occurs at the end of the fourth week.<ref name=Sadler/> Cranial and caudal neuropores become progressively smaller until they close completely (by day 26) forming the [[Biology:Neural tube|neural tube]].<ref>{{cite book|last1=Larsen|first1=W J|title=Human Embryology|date=2001|publisher=Elsevier|isbn=0-443-06583-7|page=87|edition=3rd}}</ref>
{{Clear}}

==Development of organs and organ systems==
[[File:9-Week Human Embryo from Ectopic Pregnancy.jpg|thumb|Nine-week-old human embryo from an [[Medicine:Ectopic pregnancy|ectopic pregnancy]]]]
[[Biology:Organogenesis|Organogenesis]] is the development of the [[Biology:Organ (anatomy)|organs]] that begins during the third to eighth week, and continues until birth. Sometimes full development, as in the lungs, continues after birth. Different organs take part in the development of the many organ systems of the body.

===Blood===
Haematopoietic stem cells that give rise to all the [[Biology:Blood cell|blood cell]]s develop from the mesoderm. The development of [[Biology:Haematopoiesis|blood formation]] takes place in clusters of blood cells, known as blood islands, in the yolk sac. Blood islands develop outside the embryo, on the umbilical vesicle, allantois, connecting stalk, and chorion, from mesodermal [[Biology:Hemangioblast|hemangioblast]]s.

In the centre of a blood island, hemangioblasts form the haematopoietic stem cells that are the precursor to all types of blood cell. In the periphery of a blood island the hemangioblasts differentiate into [[Biology:Angioblast|angioblast]]s, the precursors to the blood vessels.<ref name="LME">{{cite book |last1=Sadler |first1=T.W. |title=Langman's Medical Embryology |date=2010 |publisher=Lippincott Williams &Wilkins |location=Baltimore |isbn=9780781790697 |pages=79–81 |edition=11th}}</ref>

===Heart and circulatory system===
{{Further |Biology:Vascular remodelling in the embryo}}
[[File:2037 Embryonic Development of Heart.jpg|thumb|right|450px]]

The heart is the first functional organ to develop and starts to beat and pump blood at around 22 days.<ref name="Anatomy & physiology">{{cite book|last1=Betts|first1=J. Gordon|title=Anatomy & physiology|date=2013|isbn=978-1938168130|url=http://cnx.org/content/m46676/latest/?collection=col11496/latest|pages=787–846}}</ref> Cardiac myoblasts and blood islands in the [[Biology:Splanchnopleuric mesenchyme|splanchnopleuric mesenchyme]] on each side of the neural plate, give rise to the cardiogenic region.<ref name=Sadler/>{{rp|165}}This is a horseshoe-shaped area near to the head of the embryo. By day 19, following cell signalling, two strands begin to form as tubes in this region, as a lumen develops within them. These two endocardial tubes grow and by day 21 have migrated towards each other and fused to form a single primitive heart tube, the tubular heart. This is enabled by the folding of the embryo which pushes the tubes into the thoracic cavity.<ref name="Human Embryology">{{cite book|last1=Larsen|first1=W J|title=Human Embryology|date=2001|publisher=Elsevier|isbn=0-443-06583-7|pages=170–190|edition=3rd}}</ref>

Also at the same time that the endocardial tubes are forming, [[Medicine:Vasculogenesis|vasculogenesis]] (the development of the circulatory system) has begun. This starts on day 18 with cells in the splanchnopleuric mesoderm differentiating into [[Biology:Angioblast|angioblast]]s that develop into flattened endothelial cells. These join to form small vesicles called angiocysts which join up to form long vessels called angioblastic cords. These cords develop into a pervasive network of plexuses in the formation of the vascular network. This network grows by the additional budding and sprouting of new vessels in the process of [[Biology:Angiogenesis|angiogenesis]].<ref name="Human Embryology"/> Following vasculogenesis and the development of an early vasculature, a stage of [[Biology:Vascular remodelling in the embryo|vascular remodelling]] takes place.

The tubular heart quickly forms five distinct regions. From head to tail, these are the infundibulum, bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus. Initially, all venous blood flows into the sinus venosus, and is propelled from tail to head to the truncus arteriosus. This will divide to form the aorta and pulmonary artery; the bulbus cordis will develop into the right (primitive) ventricle; the primitive ventricle will form the left ventricle; the primitive atrium will become the front parts of the left and right atria and their appendages, and the sinus venosus will develop into the posterior part of the right atrium, the sinoatrial node and the coronary sinus.<ref name="Anatomy & physiology"/>

Cardiac looping begins to shape the heart as one of the processes of [[Biology:Morphogenesis|morphogenesis]], and this completes by the end of the fourth week. [[Biology:Programmed cell death|Programmed cell death]] ([[Biology:Apoptosis|apoptosis]]) at the joining surfaces enables fusion to take place.<ref name="Human Embryology"/>
In the middle of the fourth week, the sinus venosus receives blood from the three major veins: the vitelline, the umbilical and the common cardinal veins.

During the first two months of development, the interatrial septum begins to form. This septum divides the primitive atrium into a right and a left atrium. Firstly it starts as a crescent-shaped piece of tissue which grows downwards as the septum primum. The crescent shape prevents the complete closure of the atria allowing blood to be shunted from the right to the left atrium through the opening known as the ostium primum. This closes with further development of the system but before it does, a second opening (the ostium secundum) begins to form in the upper atrium enabling the continued shunting of blood.<ref name="Human Embryology"/>

A second septum (the septum secundum) begins to form to the right of the septum primum. This also leaves a small opening, the [[Medicine:Foramen ovale (heart)|foramen ovale]] which is continuous with the previous opening of the ostium secundum. The septum primum is reduced to a small flap that acts as the valve of the foramen ovale and this remains until its closure at birth. Between the [[Medicine:Ventricle (heart)|ventricles]] the septum inferius also forms which develops into the muscular interventricular septum.<ref name="Human Embryology"/>

===Digestive system===
The digestive system starts to develop from the third week and by the twelfth week, the organs have correctly positioned themselves.

=== Respiratory system ===
The respiratory system develops from the [[Biology:Lung bud|lung bud]], which appears in the ventral wall of the foregut about four weeks into development. The lung bud forms the trachea and two lateral growths known as the bronchial buds, which enlarge at the beginning of the fifth week to form the left and right main bronchi. These bronchi in turn form secondary (lobar) bronchi; three on the right and two on the left (reflecting the number of lung lobes). Tertiary bronchi form from secondary bronchi.

While the internal lining of the [[Medicine:Larynx|larynx]] originates from the [[Biology:Lung bud|lung bud]], its cartilages and muscles originate from the fourth and sixth [[Biology:Pharyngeal arch|pharyngeal arch]]es.<ref name=":0">{{Cite book|title=Langman's medical embryology.|last=Sadler |first= Thomas W. |date=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|others=Langman, Jan.|isbn=9781451113426|edition=12th|location=Philadelphia|oclc=732776409}}</ref>

=== Urinary system ===

==== Kidneys ====
Three different kidney systems form in the developing embryo: the pronephros, the mesonephros and the metanephros. Only the metanephros develops into the permanent kidney. All three are derived from the [[Biology:Intermediate mesoderm|intermediate mesoderm]].

===== Pronephros =====
The pronephros derives from the intermediate mesoderm in the cervical region. It is not functional and degenerates before the end of the fourth week.

===== Mesonephros =====
The mesonephros derives from intermediate mesoderm in the upper thoracic to upper lumbar segments. Excretory tubules are formed and enter the mesonephric duct, which ends in the cloaca. The mesonephric duct atrophies in females, but participate in [[Medicine:Development of the reproductive system|development of the reproductive system]] in males.

===== Metanephros =====
The metanephros appears in the fifth week of development. An outgrowth of the mesonephric duct, the ureteric bud, penetrates metanephric tissue to form the primitive renal pelvis, renal calyces and renal pyramids. The ureter is also formed.

==== Bladder and urethra ====
Between the fourth and seventh weeks of development, the urorectal septum divides the cloaca into the urogenital sinus and the [[Biology:Anal canal|anal canal]]. The upper part of the urogenital sinus forms the [[Biology:Urinary bladder|bladder]], while the lower part forms the urethra.<ref name=":0" />

=== Reproductive system ===
{{Main|Medicine:Development of the reproductive system}}

=== Integumentary system ===
The superficial layer of the [[Biology:Human skin|skin]], the [[Biology:Epidermis|epidermis]], is derived from the [[Biology:Ectoderm|ectoderm]]. The deeper layer, the [[Biology:Dermis|dermis]], is derived from mesenchyme.

The formation of the epidermis begins in the second month of development and it acquires its definitive arrangement at the end of the fourth month. The ectoderm divides to form a flat layer of cells on the surface known as the periderm. Further division forms the individual [[Biology:Epidermis#Layers|layers of the epidermis]].

The mesenchyme that will form the dermis is derived from three sources:
* The mesenchyme that forms the dermis in the limbs and body wall derives from the lateral plate mesoderm
* The mesenchyme that forms the dermis in the back derives from [[Biology:Paraxial mesoderm|paraxial mesoderm]]
* The mesenchyme that forms the dermis in the face and neck derives from [[Biology:Neural crest|neural crest cells]]<ref name=":0" />

===Nervous system===
{{Main|Biology:Development of the nervous system in humans |Biology:Development of the human brain}}
[[File:Human embryo 8 weeks 4.JPG|thumb|240px|Development of brain in eight-week-old embryo]]
Late in the fourth week, the superior part of the neural tube bends ventrally as the [[Biology:Flexure (embryology)|cephalic flexure]] at the level of the future [[Biology:Midbrain|midbrain]]—the mesencephalon.<ref>{{Cite journal |last=Zhou |first=Yi |last2=Song |first2=Hongjun |last3=Ming |first3=Guo-Li |date=2023-07-28 |title=Genetics of human brain development |url=https://pubmed.ncbi.nlm.nih.gov/37507490 |journal=Nature Reviews. Genetics |doi=10.1038/s41576-023-00626-5 |issn=1471-0064 |pmid=37507490}}</ref> Above the mesencephalon is the prosencephalon (future forebrain) and beneath it is the rhombencephalon (future hindbrain).

Cranial neural crest cells migrate to the [[Biology:Pharyngeal arch|pharyngeal arch]]es as [[Biology:Neural stem cell|neural stem cell]]s, where they develop in the process of [[Biology:Neurogenesis|neurogenesis]] into [[Biology:Neuron|neuron]]s.

The [[Biology:Optic vesicle|optical vesicle]] (which eventually becomes the [[Biology:Optic nerve|optic nerve]], [[Biology:Retina|retina]] and [[Medicine:Iris (anatomy)|iris]]) forms at the basal plate of the prosencephalon. The alar plate of the prosencephalon expands to form the cerebral hemispheres (the telencephalon) whilst its basal plate becomes the diencephalon. Finally, the optic vesicle grows to form an optic outgrowth.

==Development of physical features==
===Face and neck===
From the third to the eighth week the face and neck develop.

=== Ears ===
{{See also|Ear#Development}}The inner ear, [[Medicine:Middle ear|middle ear]] and outer ear have distinct embryological origins.

==== Inner ear ====
At about 22 days into development, the [[Biology:Ectoderm|ectoderm]] on each side of the rhombencephalon thickens to form otic placodes. These placodes [[Philosophy:Invagination|invaginate]] to form otic pits, and then otic vesicles. The otic vesicles then form ventral and dorsal components.

The ventral component forms the saccule and the [[Medicine:Cochlear duct|cochlear duct]]. In the sixth week of development the cochlear duct emerges and penetrates the surrounding mesenchyme, travelling in a spiral shape until it forms 2.5 turns by the end of the eighth week. The saccule is the remaining part of the ventral component. It remains connected to the cochlear duct via the narrow ductus reuniens.

The dorsal component forms the utricle and [[Biology:Semicircular canals|semicircular canals]].

==== Middle ear ====
The [[Biology:Pharyngeal pouch (embryology)#First pouch|first pharyngeal pouch]] lengthens and expands to form the '''tubotympanic recess'''. This recess differentiates to form most of the [[Medicine:Tympanic cavity|tympanic cavity]] of the [[Medicine:Middle ear|middle ear]], and all of the [[Medicine:Eustachian tube|Eustachian or auditory tube]]. The narrow auditory tube connects the tympanic cavity to the [[Biology:Pharynx|pharynx]].<ref name="Larsen2015">{{cite book |title=Larsen's human embryology |date=2015 |publisher=Elsevier, Churchill Livingstone |location=Philadelphia, Pa |isbn=9781455706846 |page=485 |edition=5.}}</ref>

The [[Biology:Bone|bone]]s of the middle ear, the [[Medicine:Ossicles|ossicles]], derive from the cartilages of the [[Biology:Pharyngeal arch|pharyngeal arch]]es. The malleus and incus derive from the cartilage of the [[Biology:Pharyngeal arch#First arch|first pharyngeal arch]], whereas the [[Biology:Stapes|stapes]] derives from the cartilage of the [[Biology:Pharyngeal arch#Second arch|second pharyngeal arch]].

==== Outer ear ====
The external auditory meatus develops from the dorsal portion of the first [[Biology:Pharyngeal groove|pharyngeal cleft]]. Six auricular hillocks, which are mesenchymal proliferations at the dorsal aspects of the first and second pharyngeal arches, form the auricle of the ear.<ref name=":0" />

===Eyes===
{{Main |Biology:Eye development}}
The eyes begin to develop from the third week to the tenth week.
[[File:Movements at gestational age of 9 weeks.gif|thumb|Movements of embryo at nine weeks gestational age]]

===Limbs===
{{main|Biology:Limb development|Biology:Limb bud}}
{{Further |Biology:Zone of polarizing activity|Medicine:Polymelia}}
At the end of the fourth week [[Biology:Limb development|limb development]] begins. [[Biology:Limb bud|Limb bud]]s appear on the ventrolateral aspect of the body. They consist of an outer layer of [[Biology:Ectoderm|ectoderm]] and an inner part consisting of mesenchyme which is derived from the parietal layer of lateral plate mesoderm. Ectodermal cells at the distal end of the buds form the [[Biology:Apical ectodermal ridge|apical ectodermal ridge]], which creates an area of rapidly proliferating mesenchymal cells known as the [[Biology:Progress zone|progress zone]]. [[Biology:Cartilage|Cartilage]] (some of which ultimately becomes [[Biology:Bone|bone]]) and muscle develop from the mesenchyme.<ref name=":0" />

==Clinical significance==
Toxic exposures in the embryonic period can be the cause of major congenital malformations, since the precursors of the major organ systems are now developing.

Each cell of the preimplantation embryo has the potential to form all of the [[Biology:Cellular differentiation|different cell types]] in the developing embryo. This [[Biology:Cell potency|cell potency]] means that some cells can be removed from the preimplantation embryo and the remaining cells will compensate for their absence. This has allowed the development of a technique known as [[Medicine:Preimplantation genetic diagnosis|preimplantation genetic diagnosis]], whereby a small number of cells from the preimplantation embryo created by [[Biology:In vitro fertilisation|IVF]], can be removed by [[Medicine:Biopsy|biopsy]] and subjected to genetic diagnosis. This allows embryos that are not affected by defined genetic diseases to be selected and then transferred to the mother's [[Biology:Uterus|uterus]].

[[Medicine:Sacrococcygeal teratoma|Sacrococcygeal teratoma]]s, tumours formed from different types of tissue, that can form, are thought to be related to primitive streak remnants, which ordinarily disappear.<ref name=Carlson/><ref name=Sadler/><ref name=Larsen/>

[[Medicine:First arch syndrome|First arch syndrome]]s are congenital disorders of facial deformities, caused by the failure of neural crest cells to migrate to the first pharyngeal arch.

[[Medicine:Spina bifida|Spina bifida]] a congenital disorder is the result of the incomplete closure of the neural tube.

[[Medicine:Vertically transmitted infection|Vertically transmitted infection]]s can be passed from the mother to the unborn child at any stage of its [[Biology:Prenatal development|development]].

[[Medicine:Hypoxia (medical)|Hypoxia]] a condition of inadequate oxygen supply can be a serious consequence of a [[Medicine:Preterm birth|preterm]] or premature birth.

== See also ==
{{div col}}
* [[Biology:Embryo loss|Embryo loss]]
* [[Biology:Aorta-gonad-mesonephros|Aorta-gonad-mesonephros]]
* [[Biology:CDX2|CDX2]]
* [[Biology:Developmental biology|Developmental biology]]
* [[Biology:Drosophila embryogenesis|Drosophila embryogenesis]]
* [[Biology:Embryomics|Embryomics]]
* [[Medicine:Human tooth development|Human tooth development]]
* List of human cell types derived from the germ layers
* [[Philosophy:Potential person|Potential person]]
* [[Biology:Recapitulation theory|Recapitulation theory]]
* [[Biology:The Human Embryo|The Human Embryo]]
{{div col end}}

==Additional images==

<gallery>
File:Didactic model of a human embryonic development 01.jpg|Representing different stages of embryogenesis
File:Didactic model of a human embryonic development 05.jpg|Early stage of the gastrulation process
File:Didactic model of a human embryonic development 03.jpg|Phase of the gastrulation process
File:Didactic model of a human embryonic development 04.jpg|Top of the form of the embryo
File:Didactic model of a human embryonic development 02.jpg|Establishment of embryo medium
File:Sobo 1909 621.png|Spinal cord at five weeks
File:Gray947.png|Head and neck at 32 days
</gallery>

== References ==
{{reflist}}

== External links ==
* [https://www.ehd.org/virtual-human-embryo Virtual human embryo]
* [https://www.pbs.org/wgbh/nova/miracle/images/stem_blastocyst.jpg Photo of blastocyst in utero]
* Slideshow: [https://web.archive.org/web/20161222152312/http://www.lifehugger.com/doc/99/womb In the Womb]

{{Embryology}}
{{Developmental biology}}

{{DEFAULTSORT:Human Embryogenesis}}
[[Category:Embryology]]

{{Sourceattribution|Human embryonic development}}