Gastrulation/Neurulation Flashcards
What is gastrulation?
What is the state of the embryo when it occurs? What is its orientation?
How does gastrulation begin and end? Where is cell fate determined?
What are the first membranes to form?
Gastrulation is the process that begins at around day 14 and creates the definitive germ layers from the epiblast during 3rd week of development.
At 14 days the embryo is suspended by an extraembryonic mesodermal stalk within the chorionic cavity. The embryonic disc consists of two simple layers, epiblast and hypoblast, separating the amniotic and yolk sac cavities. (The epiblast is dorsal and the hypoblast is ventral)
Gastrulation begins with the appearance of the primitive streak in the epiblast at the caudal pole of the bilayered embryonic disc.
Cells of the epiblast migrate over the dorsal side of the disc and down into the primitive streak, becoming flat as they slip beneath it in a movement known as invagination. These epiblast cells emerge below and move toward destinations that are roughly equivalent to their former positions in the epiblast.
Once the cells have invaginated, some displace the hypoblast, creating the endoderm, and later others come to lie between the epiplast and the newly created endoderm to form the mesoderm. Cells remaining in the epiplast then form ectoderm.
The primitive node forms at the cephalic end of the streak. The node is an important determinant of cell fate and influences the subsequent differentiation of epiplast cells as they pass into and through its field of influence, becoming either part of the endoderm or ectoderm.
The oropharyngeal (at the cephalic end) and the cloacal (at the caudal end) membranes mark the future positions of the anterior and posterior openings of the gut tube.
How must cells change in order to form the endoderm during gastrulation?
When is another time this change occurs? How is it clinically relevant to adults?
Epithelial-mesenchymal transition: Epithelial cells detach from one another and become migratory (mesenchymal) cells in order to leave the epiblast and migrate between the epiblast and hypoblast.
They reacquire epithelial character as they form the endoderm.
This process repeats during neural crest development AND it is a critical step in the evolution of epithelial tumors (adenomas) into metastatic carcinoma.
What is the significance of oropharyngeal and cloacal plates?
The oropharyngeal and cloacal membranes mark the future positions of the anterior and posterior openings of the gut tube. They form where the ectoderm and endoderm meet.
Oropharyngeal membrane at the cephalic end
Cloacal membrane at the caudal end
How are the lateral body axes established, particularly leftsideness and rightsideness?
Left-right asymmetry along the longitudinal body axis is established by asymmetric expression of growth determinants in the region of the primitive node.
There is now good evidence that the beating of cilia (inset) on the surfaces of cells in the nodal region in a right-to-left direction sets up a fluid flow that causes left-side accumulation of the asymmetry determinant molecules. Later on, we’ll see that there are specific factors localized on the right side of the embryo that also determine asymmetric positioning of the heart toward the left side.
Normally, many organs exhibit asymmetries, including the heart, lungs, gut, spleen, stomach, liver, and others. Positioning these organs and establishing their asymmetries is orchestrated by a cascade of signal molecules and genes. When the primitive streak appears, FGF8 is secreted by cells in the node and primitive streak, and this growth factor induces expression of NODAL (Fig. 5.6A). NODAL expression is then restricted to the left side of the embryo by the accumulation of serotonin (5-HT) on the left side. These high concentrations of 5-HT on the left activate expression of the transcription factor MAD3 that restricts NODAL expression to the left side of the primitive node (Fig. 5.6-B). Midline genes like SONIC HEDGEHOG {SHH), LEFTYl, and ZIC3 (a gene on the X chromosome that codes for a zinc finger transcription factor) are involved in establishing the midline but also prevent NODAL expression from Crossing over to the right side. Ultimately, Nodal protein in the left lateral píate mesoderm initiates a signaling cascade that in- cludes LEFTY2 to upregulate PITX2 (Fig. 5.6B). PITX2 is a homeobox-containing transcription factor that is a “master gene” responsible for establishing left-sidedness, and its expression is repeated on the left side of the heart, stomach, and gut primordia as these organs are assum
ing their normal asymmetrical body positions. If the gene is expressed ectopically (e.g., on the right side), this abnormal expression results in laterality defects, including situs inversus and dextrocardia (placement of the heart to the right side; see “Clinical Correlates,” p. 65).
Why the cascade is initiated on the left remains a mystery, but the mechanism may involve cilia on cells in the node that beat to create a gradient of Nodal toward the left or by a signaling gradient established by gap junctions and small ion transport.
How and when is the notochord formed?
How does this determine the cells that surround the notochord?
Visualize the positioning of notochord, paraxial, intermediate, and lateral plate mesoderm
In a midline section of the entire 17-day embryonic disc, the mesoderm directly ahead of the primitive pit differentiates into the notochord (extending in a forward direction, towards the cephalic end).
Later the notochord separates from the ectoderm and endoderm, creating a midline with mesoderm cells on either side. The location of the mesoderm cells with respect to this midline deremines what tissues they will later form. Thus the notochord is flanked by intra-embryonic mesoderm.
What is neurulation and when/where does it begin?
What is the initial event of neurulation?
How is the closed neural tube formed and what will it become?
How are somites formed and from what germ layer?
When is neurulation complete?
Neurulation is the process whereby the neural plate (formed as the overlying ectoderm thickens with the appearance of the notochord and prechordal mesoderm) form the neural tube AND the primitive body form is discernible as the embryo changes from a plate to a more tubular form within the amniotic cavity.
Neurulation begins in the head region late in the 3rd week.
During neurulation (which progresses caudally) the neural plate lengthens by a lateral to medial movement of cells in the plane of the ectoderm and mesoderm.
As the neural píate lengthens, its lateral edges elevate to form neural folds, and the depressed midregion forms the neural groove. Gradually, the neural folds approach each other in the midline, where they fuse. Fusión begins in the cervical región (fifth somite which will eventually be the region of the hind-brain and neck) and proceeds cervically and caudally to form a closed neural tube first at the cranial neuropore then at the posterior neuropore.
Mesodermal somites coalesce on either side of the neural tube just below the ectoderm, where they are visualized as protrusions or bumps in the ectoderm.
Where do somites form? What germ layer are they from? What do they give rise to?
What happens to mesoderm that doesn’t form somites?
From which germ layer is the visceral layer around organs derived?
The mesodermal layer surrounds either side of the notochord. The cells closest to midline proliferate and form a thickened plate of tissue known as the paraxial mesoderm. (Lateral mesoderm = lateral plate. Paraxial mesoderm = somitomeres and neuromeres. Somitormeres = somites)
Concentrated mesodermal cells in the occipital region caudually organize into somites. From here, new somites appear in craniocaudal sequence (Fig. 6.10) at a rate of approximately three pairs per day until, at the end of the fifLh week, 42 to 44 pairs are present (Figs. 6.4B and 6.10). There are 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8 to 10 coccygeal pairs. The first occipital and the last five to seven coccygeal somites later disappear, while the remaining somites form the axial skele- ton (see Chapter 10). Because somites appear with a specified periodicity, the age of an embryo can be accurately determined during this early time period by counting somites.
When somites first form from presomitic mesoderm, they exist as a ball of mesoderm (fibroblast- like) cells. These cells then undergo a process of epithelization and arrange themselves in a donut shape around a small lumen. By the beginning of the fourth week, cells in the ventral and medial walls of the somite lose their epithelial characteristics, become mesenchymal (fibroblast-like) again, and shift their position to surround the neural tube and notochord.
Collectively, these cells form the sclerotome that will differentiate into the vertebrae and ribs.
Cells at the dorsomedial and ventrolateral edges of the upper región of the somite form precursors for muscle cells, the myotome, whereas cells between these two groups form the dermatome. Cells from both muscle precursor groups become mesenchymal again and migrate beneath the dermatome to create the dermo- myotome individual layers.
sclerotome = axial skeleton, dermatome = dermis, and myotome = muscle
Mesoderm that isn’t paraxial forms the lateral plate which becomes (1) somatic or parietal mesoderm layer (2) splanchnic or visceral mesoderm layer
From what germ layer does the gut tube arise?
Which germ layers form the lateral body wall folds? What layers divide the primitive body cavity?
Why is the phrenic nerve (function?) originate in the cervical segments when most of the diaphragm is in the thorax?
The visceral layer rolls ventrally and is intimately connected to the gut tube; the parietal layer, together with the overlying ectoderm, forms the lateral body wall folds (one on each side of the embryo), which move ventrally and meet in the midline to cióse the ventral body wall (Fig. 7.1). The space between visceral and parietal layers of lateral píate mesoderm is the primitive body cavity, which at this early stage is a continuous cavity, because it has not yet been subdivided into the pericardial, pleural, and abdominopelvic regions.
Together, the parietal (somatic) layer of lateral píate mesoderm and overlying ectoderm are called the somatopleure; (2) the visceral (splanchnic) layer adjacent to endoderm forming the gut tube and continuous with the visceral layer of extraembryonic mesoderm covering the yolk sac (Figs. 7.IB). Together, the visceral (splanchnic) layer of lateral píate mesoderm and under- lying endoderm are called the splanchnopleure. The space created between the two layers of lateral píate mesoderm constitutes the primitive body cavity. During the fourth week, the sides of the embryo begin to grow ventrally forming two lateral body wall folds (Fig. 7.IB and C). These folds consist of the parietal layer of lateral píate mesoderm, overlying ectoderm, and cells from adjacent somites that migrate into the mesoderm layer across the lateral somitic frontier.
By the end of 4 weeks, the primitive ”tadpole-like” body form of the embryo lying within the amniotic cavity is apparent with the definition of the pharyngeal arches. With the folding of the lateral body walls downward, part of the old yolk sac is incorporated into the embryo as the endodermal gut tube and the extra-corporeal portions of the yolk sac persist temporarily within the constricted umbilicus.
Note the transient continuity of the intra-embryonic (paraxial and intermediate) mesoderm with the extra-embryonic mesoderm the amniotic and yolk sac cavities.
You can now see how the early cardiac region (angiogenic cell cluster), previously located anterior to the developing brain, becomes folded into the thorax as the pericardial cavity. Note also how the pendant yolk sac is pinched off in the umbilicus from the elongating gut tube that now lies within the folded embryo.
Phrenic nerve supplies sensory and motor fibers to the diaphragm. During the fourth week the septum transversum, which forms the central tendon of the diphragm, lies opposite cervical segments three to five. As the embryo grows the the head curves ventrally, the position of the septum transversum (diaphragm) shifts into the thoracic cavity. Musculature for the diaphragm is derived from the original cervical segments and since muscle cells always carry the nerve from their site of origin to wherever they migrate, it is the phrenic nerve from C3-C5 that innervates the diaphragm.
Which cells form the barrier between maternal and fetal blood? What is their role?
How and where is gas and nutrient exchange established with the maternal blood?
Note that at the end of the 3rd week, the tertiary stem villi have pushed through the lacunae and are now beginning to line the entire external surface of the placenta with cytotrophoblast.
Embryonic blood vessels and extra-embryonic mesoderm are pushing into the stem villi to establish gas and nutrient exchange with the maternal blood in the trophoblastic villi (end of 3rd week).
Note that syncytiotrophoblast, cytotrophoblast, extra-embryonic mesoderm, and embryonic vessel walls (endothelium) form the barrier between maternal and fetal blood. These layers will play active roles in transport of proteins such as immunoglobulins from maternal to fetal blood.
The fetal component of the placenta is derived from the trophoblast and extraembryonic meso- derm (the chorionic píate); the maternal component is derived from the uterine endometrium. By the beginning of the second month, the trophoblast is characterized by a great number of secondary and tertiary villi, which give it a radial appearance (Fig. 8.7). Stem (anchoring) villi ex- tend from the mesoderm of the chorionic píate to the cytotrophoblast shell.
Beginning at the 2nd month, the placenta englarges at the embryonic pole. At this stage the embryo is still relatively small within the chorionic cavity.
How does the placenta develop? From which spaces?
How many and which cavities close at the end of the 3rd month?
Where in the developing fetus can stem cells be taken? What is an alternative source of stell cells?
Trace the development of amniotic, chorionic, & uterine cavities into the fetal period.
By the end of the 3rd month, the amnion and chorion have fused, and the uterine cavity is obliterated by fusión of the chorion laeve and the decidua parietalis. the expanding amniotic cavity containing the fetus has essentially obliterated the chorionic cavity, and the expanding amniotic sac is filling the uterine cavity (note – you do not need to learn the names of the specific tissue layers at this time).
2 cavities close: (1) chorion cavity by chorion laeve and amnion fusing (2) uterine cavity by chorion laveae and uterine lining (decidua parietalis) fusing.
The umbilical cord, because it encloses the yolk sac and the stem cells that give rise to primordial germ cells and blood cells, can itself be a source of stem cells that can be drawn on later for experimental or therapeutic uses if the cord is saved and stored frozen after parturition.
What organs are derived from the gut endoderm?
Whar are their endodermal derivatives?
You should note the locations of the endodermal derivatives, including pharyngeal pouches, lung buds, liver, gall bladder, stomach, pancreas, primitive intestinal loop, hindgut, and bladder, as the further development of all these organs will be covered in subsequent lectures.
What are the components of the mesodermal core of the tertiarly placental villi?
What is the role of the yolk sac?
Note that the yolk sac, in addition to providing primitive germ cells, is a major source of blood cells and vessels that connect the embryo to the placenta through the umbilicus.
