Embryology Flashcards
Two reactions that happen in sperm in the female reproductive tract
- Capacitation: revealing of the receptors, removal of glycoprotein coat AND seminal plasma proteins, it is needed to pass through the Corona cells
- Acrosome reactions: Sperm sticks to ZP, facilitated by ZP3 protein, ZP is penetrated, sperm enters the plasma membrane of the oocyte
The ZP3 is a ligand for sperm recepters, allows the release of enzymes from the acrosome
What is done to avoid polyspermy
There are 2 reactions that happen to avoid this: cortical reactions (release of lysosomes from the cortical granules) and zona reactions where the ZP’s chemical properties are changed to avoid further binding AND penetration
Oocyte membrane also becomes impenetrable
What is the name of the structure that forms after fertilization
Zygote
What happens at the 8 cell stage
Compaction, maximizing cell to cell contacts
What is the structure called at 16 cell stage
Morula, it now enters the endometrium lumen
What is the necessary for implantation
Loss of ZP
What does the inner and outer cell mass form in a blastocyst
Amnion, yolk sac and embryo proper
Trophoblast
When does implantation occurs
On the 6th day
What does corpus luteum make
Progesterone to preserve the endometrium lining
Explain the mechanism of pregnancy stick
Synccyteotophoblast cells make Human Chorionic Gonadotrophin hormone, it is detectable by week 2
What happens after the stage when trophoblast cells allow implantation of the blastocyst
The next stage is characterized by the formation of lacunae in syncytotrophoblast cells and the formation.
Know that the exocoelomic cavity and the membrane is still present and the exocoelomic membrane is also called the Heuser’s membrane
What happens after the stage when lacunae develops in syncyteo
Heuser’s membrane have pores called extraembryonic cavity. The part of the membrane in contact with the exocoelomic cavity is called the extraembryonic splanchnopleuric mesoderm and the one that is on the other side of the extraembryonic cavity is the extraembryonic somatopleuric mesoderm
Where are the splanch and somato mesoderms when the (exocoelomic cyst) primitive yolk sac is pinched off and the chorionic membrane surrounds the fetus
The splanchno is surrounding the fetus whereas the somato is now surrounding the chorionic cavity
What lines the secondary yolk sac
Extraembryonic endoderm which in turn is lined by splanchno
What are the two cell layered structures that form at this stage
Primary villi
What happens on day 13 and day 28
Uteroplacental circulation starts and bleeding occurs which can be mistaken for a period, respectively
Name the 3 abnormal implantation sites
Mesentry, oviduct (or uterine tube) and ovary
Where does most of the ectopic pregnancies occur
In the oviduct, in the ampulla region (the wider lumen region)
What other region is common for ectopic pregnancy.
What are the risks involved?
Rectouterine pouch, attached to the peritoneum.
Surgery may involve hemorrhage.
What are the two membranes that lie on the opposite poles of the primitive node and primitive streak
Buccopharyngeal membrane that will form the oral cavity and the cloacal cavity that will form the rectum (or anus or whatever).
What are prenotochordal cells
Cells that migrate to form notochord eventually. These cells move through the primitive node
When does the trilaminar germ disc layer formation occur
Day 15 or 16, this is when the cells start to migrate
What is the fate of hypoblast cells
They can either contribute to heuser’s membrane or they can be a part of the extraembryonic endo and mesoderm
What is a fate map of epiblast cells
The length through which they enter the primitive streak (or the primitive node so to speak) determines what structures will they differentiate into
How does the notochord forms
In a cranial to caudal fashion
What is alantois
It plays a role in blood vessel development in the connecting stalk
What happens before the formation of notochord
Notochord plate forms
When are the body axes established
The establishment of body axes occur right before gastrulation
What is anterior and posterior
Anterior is head, posterior is tail
How does the anterior-posterior axis develops
First we will talk about the formation of head region. It is formed by the cells in the anterior region called the Anterior Epiblast cells. These express genes responsible for the formation of head region and this also avoids formation of primitive streak in the head region.
The cranial end of the embryo is established before gastrulation.
Primitive node is responsible for maintaining the primitive streak which by the help of transforming growth factor beta family specializes the caudal portion.
The node secretes goosecoid, chordin, noggin, follistatin and nodal.
How is the dorsal and ventral axis established.
Define this axis in the embryo first.
Dorsal is towards the neural tube and ventral is towards the notochord.
Bone Morphogenic Protein 4 (BMP4) ventralizes the Mesoderm (Intermediate and Lateral Plate Mesoderm).
Chordin (activated by Goosecoid), noggin, follistatin (secreted by node) antagonizes the BMP4 so it results in dorsalizing the cranial mesoderm forming the notochord and paraxial mesoderm.
Further details on what is the role of dorsal-ventral axis
The establishment of dorsal and ventral axis results in the formation of notochord. Notochord later secretes dorsalizing factors (chordin, noggin, follistatin).
Brachyury gene expressed in the node, prenotochordal and notochordal cells dorsalizes embryo in the middle and caudal region.
So dorsalization of the head happens first.
Any pathologies relating to ventral-dorsal axis?
Goosecoid regulates head development, under or over expression can lead to pathology that of cojoined twins.
Chordin is activated by Goosecoid.
Function of Brachyury gene
It is important in migration of the cells through the primitive streak and dorsalizing the caudal region.
Pathology associated to brachyury gene
Caudal dysgenesis or Sirenomelia. There is shortening of embryo leading to caudal region malformation by fusion of the limb buds.
How do you establish the left and right axis
The primitive node secretes FGF8 (fibroblast growth factor 8) on the left, that activates nodal that causes left sidedness. It is absence of FGF8 that causes the right side to develop. Sonic Hedge Hog suppresses the left sided genes on the right side.
The left and right side are formed with respect to the notochord.
Also ciliated cells play an important role in the left-right axis formation.
These ciliated cells rotate and establish flow patterns.
Describe the progress of gastrulation along the body of the embryo
Gastrulation occurs cephalocaudally which means it occurs first in the cephalic region and then it starts later in the caudal region. . Primitive streak regresses from the middle to the caudal region
Embryonic disc expands (I think they are talking about the head) as cells continuously migrate from the primitive streak to the cranial region.
What are teratogenic insults
Hypersensitivity to teratogenesis, begins on the 3rd week. The associated pathologies are:
1. Holoprosencephaly - craniofacial defects due to the consumption of high amounts of alcohol.
2. Caudal dysgenesis (sirenomelia)
3. Situs Inversus - Transposition of viscera in thorax and abdomen
4.
Tumors associated with gastrulation
Sacrococcygeal Teratoma which arises due to remnants of the primitive streak. These usually are not malignant.
Types of villi, when do they form and what are their structures
Primary - 2 cell thick (cyto and syncyteo)
Secondary - primary structure + mesoderm core
Tertiary - secondary structure + blood vessels but there is depletion of cyto layer.
These form at the end of 3 weeks.
Does the blood of mother and fetus mixes up?
No, it never does due to the presence and development of placenta through which exchange takes place.
Describe the structure of placenta
The layer which is in contact with maternal blood is the syncyteo but the highest layer on top is cyto.
Chorionic plate separates the bulk of connecting stalk from the maternal blood.
When does fetal heart beat start
At the end of 4th week
It is detectable by 6th week
How does the fetus look like at the end of 3rd week
Know where the following is
Chorionic cavity, exocoelomic cyst, definitive yolk sac, amnion, syncyteum (the syncyteo layer).
What are the derivatives of ectodermal layer (there are 6)
- Central nervous system
- Peripheral nervous system
- Sensory epithelium of the nose, ear and eye
- Epidermis, hair and nails
- Mammary, pituitary and subcutaneous gland
- Neural crest cells
Describe the formation of neural plate
Notochord and prechordal mesoderm secrete chordin, noggin, follistatin to dorsalize the ectoderm and induce the formation of neural plate.
The neural plate curls up to form neural folds. Then it forms the neural tube.
It is the neuroectoderm that is induced by the notochord.
How is the formation of neural tube regulated
It is regulated by the gradient of BMP4.
At max [BMP4] the ectoderm is dorsalized to become the epidermis.
At medium [BMP4] neural crest cells are formed
At low [BMP4] achieved by dorsalizing factors chordin, noggin and follistatin from notochord, the ectoderm is neurulized resulting in neural plate formation.
How does the forebrain, mid brain and hind brain situate themselves
Along the neural tube, starting from the cephalic region and going to the caudal region slightly.
Explain the progress of development of the neural tube
At day 22 there is bidrectional fusion of the neural folds that gives rise to neural tube later. Situated in this sturcture the anterior and posterior neural pores and the somites which is basically the dorsalized mesoderm.
Where does the somites arise from
Differentiate from paraxial mesoderm
What is the first visible structure visible immediately after bidirectional fusion of neural folds
The pericardial bulge that later develops to become a heart
When does the completion of neurelation occur? what structures are visible?
At day 28.
Pericardial bulge, lens placode and otic placode. Also visible are the pharyngeal arches.
Important developmental points in the growth of the embryo. What pathological conditions are associated with these?
Close of the anterior and posterior pore that happen at day 25 and day 28 respectively. The two pathological conditions are Anencephaly and spinal bifida.
These malformations can be avoided by the use of folic acid. The diseases can also be checked by alpha fetoprotein, high levels of this protein can help diagnose these malformations together with ultrasound imaging.
Explain the formation of neural crest cells. What cells to they differentiate into?
They lie between the non neuralized (epidermis) and neuralized ectoderm where the levels of BMP4 are athe medium level. These cells differentiate into:
- Melanocytes
- Craniofacial cartilage and bone
- Smooth muscle
- Preaortic ganglia
- Sympathetic chain
- Schwann cells (glial cells in the PNS)
These cells are multipotent and transient
Explain the role of neural crest cells in further development of the fetus
As the neural tube closes, these cells undergo epithelial to mesechymal transition and settle themselves in the mesoderm
What do neural cells do in the head and trunk region
In the trunk region they form:
- Melanocytes
- Sensory Ganglia
- Adrenal Medulla
- Enteric Neurons
- Schwann cells
In the head region these cells migrate to phanryngeal pouches and constitute to the development of craniofacial features.
They give rise to
- Neurons
- Glia cells
- Cartilage and bone
- Connective tissue
What are the underlying reasons for craniofacial anomalies
Neural crest cells not differentiating or executing their function properly.
Comments on Hox genes
To wrap up ectoderm we talk about hox genes. Hox genes are present in chromosomes in clusters, they were discovered in drosophila and then in mice. These genes that are of similar color (lie in the same corresponding position on a different chromosome) are called paralogous genes. There are usually found in clusters. These genes code for transcription factors that activate gene cascades regulating segmentation identity, so they determine what structure from from what segments.
Hox genes that are at the closer 3’ end are usually expressed first and they code for the development of head regions such as different part of brain.
Explain the formation of brain with the aid of the concept of Hox genes
Notochord, prenotochordal plate and neural plate signals brain segragation into fore, mid and hind brain. Then hox genes kick in and confer positional information in the brain, like formation of sections inside the forebrain, the midbrain and the hindbrain
What does the endoderm differentiate into
Epithelial lining of the GI, respiratory tract, urinary bladder, auditory tube, liver, pancreas and cloaca
Explain the phenomena of gut formation
There is cephalocaudal (head to tail) folding of the embryo that leads to gut formation. This folding is more pronounced in the head and tail region. Due to cephalocaudal folding the amnion now covers the entire embryo after sitting on top of the embryo for so long..
Allantois and mesoderm later contribute to the development of blood vessels in the connecting stalk.
The folding promotes the endoderm-lining of the cavity to be incorporated into the body of the embryo for gut formation.
There is also lateral folding that results from the rapid growth of somites. The gut forms a tube (looks like laterally) and the ventral body wall is established. Midgut still has the connection to yolk sac forming the vitelline duct.
On the slide she said at 10 weeks, intestinal loops are herniated into yolk sac duct (not yolk sac) and they are in the umbilical cord, due to size constraints of the abdominal cavity. These have their associated pathologies.
Explain the anatomy of the developing gut
Buccopharyngeal membrane lines the foregut whereas the cloacal membrane lines the hindgut until each of their ruptures. The mid gut remains connected with the yolk sac and this is where the small intestine initially form.
Allantois sticks out in the connecting stalk.
How are the segments of the gut determined
Gut region specifications begins when the lateral body wall folding brings 2 sides of the gut tube together. This is another example of hoax genes. Once the segments of the gut are specified, the mesenchymal cells expressing hoax genes secrete Sonic Hedge Hog (SHH) factor. They determine the small intestine, large intestine, column and saecum
Gut endoderm secretes SHH
Splanchnic mesoderm expresses hox genes
Genetic cascade leads to segmentation of the gut
How does the lung and trachea form
Epithelial lining of the larynx, trachea, bronchi and lungs is endodermal in origin. Lungs are formed when the ventral wall of the gut out buds to form the Respiratory dierticulum.
Trachea forms from tracheaesophegal septum
Where does the intraembryonic coelom come from. What structures does it give rise to
From the cavities that form in the lateral plate mesoderm. It gives rise to splanchnic and somatic mesoderm (splanchnic is on the bottom whereas somatic is on the top, later somatic lines the organs of the embryo (visceral) and splanchnic lines the yolk sac (parietal))
Which parts of the mesoderm are ventralized and dorsalized
Paraxial is dorsalized, the rest of the two are ventralized
What structure if formed from the folding of the mesoderm
Intraembryonic cavity, which then is seperate from the extraembryonic cavity
What does the 3 parts of mesoderm give rise to
- Paraxial gives rise to somites which then form: vertebrae, ribs, dermis of the dorsal skin, skeletal muscles of the back, skeletal muscles of the body wall and limbs
- Intermediate mesoderm gives rise to urogenital structures.
- Lateral plate mesoderm form the heart and blood vessels and the body walls
So remember that paraxial gives rise to skeletal muscles and LPM gives to cardiac and smooth muscles
Explain the process of somites formation
Paraxial mesoderm starts to arrange itself into balls called somitomeres.
The formation of somitomeres happens cephalocaudally.
It is worthwhile to mention that the head formation happens so fast that the somitomeres in the cephalic region dont even get enough time to form somites and they already start contributing mesenchyme cells for head formation.
How is the somite formation regulated
It is regulated by cyclic genes and growth factors
Describe the structure of somites
They occur in pairs, from occipital to coccygeal region, their position determines what structure will they differentiate into.
What structures does somites form and then what does those structures then form?
We then talked about the significane of segmentation of somites. Each somite forms:
1. Scelrotome: Sclera means something hard, ribs, vertebrae, ribs, cartilage
- Myotome: myo means muscle so they form muscles of the back, the body wall (intercostal muscles) and some limb muscles.
- Dermatome: dermis of the back (skin of the back)
- Ventrolateral cells: Most of the musculature for body wall (obliques, transverse abdominus) and limbs.
Somites determine the spinal axon paths and neural crest cells migration paths
How does somites contribute to the development of other structure that arise from cells other than that of somites
Somites determine the spinal axon paths and neural crest cells migration paths
Explain how the paraxial mesoderm form into somites
On the 4th week the paraxial mesoderm forms into a donut like structure. Above it are loose suspended cells of the sclerotome whereas above the scleretome is dermatome surrounded by ventrolateral muscles cells and dermomedial muscle cells.
The the cells in the two muscle groups migrate below the dermatome to form myotome and the sclerotome still appears as loose suspended cells.
The structure formed by dermotome and myotome is called the dermomyotome.
It is important to know that a subset of cells from the ventrolateral muscle group migrates to LPM to form muscles of the body wall and limbs.
What is secreting the dorsalizing and ventralizing molecules
Dorsalizing - Neural tube (upper region)
ventralizing - Notochord
Name one structure that somites and neural crest cells differentiate into.
What do these structures form later
Somites together with neural crest cells form pharyngeal arches. These pharyngeal arches later differentiate into craniofacial features so they give rise to face, mouth, head, larynx and pharynx.
To form these features they also form muscles, blood vessels, connective tissue, cartilage, bone.
Name similar structures that are formed from ectoderm and endoderm
Pharyngeal grooves or lefts are formed by ectoderm whereas pharyngeal pouches are formed by the endoderm.
How many pairs of pharyngeal arches are there in the fetus
5
What does intermediate mesoderm form
Urogenetical structures; this includes kidneys, gonads and their associated ducts
Explain the formation of urinary structures and their associated ducts
First we have pronephric that is in the caudal region, then we have mesonephric towards the middle and finally we have metanephric excretory cells that later differentiate to form out kidneys. These cells lie in the caudal region.
All of these structures can have overlapping functions during development.
The excretory ducts of the kidney and gonads enter the cloaca which is a common drainage site
Explain the formation of genital structures: what cells give rise to this structure, where do they go and where is this structure located
Premordial cells give rise to genital structures. These cells themselves are derived from epiblasts.
They form genital structures by migrating to the hind of the yolk sac in the structures called genital ridge that lie on the mesonephro structure.
After migration, these cells induce the formation of ovaries or testes.
Explain the contributory role of LPM during the 3rd week
Leads to lateral folding giving seperating the intraembryonic space from the extraembryonic space. Also there is a rise of 2 different mesoderms called the splanchnic mesoderm and the somatic mesoderm. Somatic (parietal) mesoderm covers the organs (covers somites) and splanchnic covers the yolk sac (visceral).
How does these layers look like when the embryo is cut in cross section.
How does the gut look like
They look different. Parietal surrounds in turn the visceral.
Gut looks like a tube
How is the heart formed.
What is common between the formation of gut and formation of the heart.
Formation of gut and formation of the heart happens at the same time.
The heart is formed by precursor cells called the endocardial mesoderm which lies below the myocardial mesoderm.
Cross sectional folding of LPM results in the formation of endocardial tube.
Describe the anatomy of early heart
Early heart lies right under the foregut in the cephalic region. It is made of myocardium on the outside adn endocardium in the inside, the space between these 2 cells is filled with cardiac jelly.
This structure is surrounded by pericardial cavity.
This tube is connected to the rest of the embryo by dorsal mesocardium.
The amnion cavity at this stage completely surrounds the embryo.
Blood formation
These arise from the splanchnic layer of mesoderm and from extraembryonic mesoderm.
These cells are induced to become hemangioblasts by FGF2 (these cells have FGF2 Receptor). These hamangioblasts are then induced by VEGF (vascularizing endothelial growth factor) to become blood islands which are hematopoietic cells and angioblasts. This leads to the formation of vasculogenesis and angiogenesis.
Describe the difference between vasculogenesis and angiogenesis
Angiogenesis is the formation of branches from existing blood vessels and vasculogenesis is the formation of blood vessels from scratch (from precursor cells).
Where are the sites of blood vessels formation
First ones form in the yolk sac.
Extraembryonic mesoderm leads to the formation of blood vessels in the walls of the yolk sac.
Within the extraembryonic mesoderm the somatic mesoderm vasculorizes first and then the splanchnic.
Intraembryonic mesoderm then sets up blood vessels.
Remember extra happens first and then its intraembryonic mesoderm leading to blood formation
Pathology in vasculorization.
What are they called?
Describe them.
These are called capillary hemagiomas. They can be diffused or focal
Describe the process of hematopoiesis in the fetus along its development
Extraembryonic mesoderm leads to the formation of blood capillaries in the yolk sac around week 3.
Aorta Gonad Mesonephro cells form (AGM)
AGM migrates to the liver later and takeover the process of hematopoiesis from 2nd month to 7th month.
Cells from the liver colonize bone marrow in the 7th month of gestationand take over the responsibility of hematopoiesis for the rest of our lives
How do we monitor the growth of the embryo
We use crown-rump length. It is in millimeters.
Name another important structure that the lateral plate mesoderm form
Limbs!
These are derived from LPM.
Describe the formation of limb
These are outpiocketings from the ventrolateral body.
Forelimbs appear 1 to 2 days before hind limbs. The core of the limbs is from mesenchyme that develops into bone and connective tissue.
Where are future limb skeletal muscles derived from
Paraxial mesoderm
What process is responsible for digit formation
Apoptosis - has to be well organized and well executed.
Pathology associated with digit formation
Syndactylyl - fused limbs due to improper or incomplete apoptosis.
