FOM: week 6 Flashcards
What is a morula?
A morula is an early embryo that has approximately 16 spherical cells (blastomeres) and divides into inner and outer cells
Where do the first few cell divisions of the embryo occur?
The first cell divisions occur in the oviduct as the embryo travels to the uterus (usually takes 6-7 days for the zygote to travel to uterus)
What is the significance of the inner and outer cells of the morula?
After compaction, the morula divides into two layers of cells: inner gives rise to embryo, and outer gives rise to extraembryonic tissues (including the placenta)
What is compaction?
Compaction occurs when the blastomeres within the morula flatten into a tight ball and become polarized. Fluid fills the space where the non-condensed blastomeres used to be. The embryo is now called a blastocyst.
When and where does implanation occur?
Implanation involves the attachment and embedding of a zygote into the uterine lining. It usually occurs roughly 6-7 days after fertilization and is initiated by hatching. Implantation typically occurs in the posterior wall of the uterine cavity.
What is ectopic pregnancy?
Ectopic pregnancy is the implantation of an embryo in an atypical location.
What are two common sites of ectopic pregnancy?
- ampulla of oviduct 2. close to cervix – results in placenta previa which causes hemorrhaging and threatens the survival of the mother and fetus.
What is hatching and what does it do to the zona pellucida?
Hatching occurs about 6-7 days after fertilization and involves the degradation of the zona pellucida by hydrolytic enzymes released from the trophoblast cells of the embryo. Degrading the zona allows the syncytiotrophoblast cells to penetrate the uterine lining and implant themselves.
How does the bilaminar disc form?
The bilaminar disc forms from the inner cell mass of the blastocyst. Fluid appears between the inner cells and separates them from the trophoblast into two regions: epiblast and hypoblast.
What are epiblasts and what do they eventually become?
Epiblasts are tall columnar epithelia that hold the amniotic fluid. These eventually give rise to the embryo proper and some extraembryonic structures.
What are hypoblasts and what do they eventually become?
Hypoblasts are cuboidal epithelia that become the yolk sac. The yolk sac eventually gives rise to extraembryonic structures like the connecting stalk which becomes the umbilical cord.
What is gastrulation and when does it occur?
Gastrulation is termed as the migration of epiblast cells to form three distinct layers: ectoderm, mesoderm, and endoderm. This process occurs in the third week of development.
What is the primitive streak?
The primitive streak is a result of epiblast cells that are oriented rostral to caudal. Epiblast cells migrate ventrally through the primitive streak and form embryonic endoderm (most ventral cells) and mesoderm (cells that reside between epiblast and hypoblast cells).
What is the primitive node and what structure does it form?
The primitive node forms at the rostral end of the primitive streak and has epiblast cells that descend through it to form a thick cord of cells called the notochord.
What are the two main functions of the notochord?
- Lends mechanical support to embryo 2. serves as a powerful inductive force for subsequent cell differentiation (organizing center)
What major body structures result from ectoderm?
Epidermis, hair, nails, cutaneous and mammary glands; central and peripheral nervous system
What major body structures result from mesoderm?
Paraxial: form somites that become muscles of head, trunk, limbs, axial skeleton, dermis, connective tissue; Intermediate: Urogenital system, including gonads; Lateral: Serous membranes of pleura, pericardium, and peritoneum, connective tissue and muscle of viscera, heart, blood cells
What major body structures result from endoderm?
Epithelium of lung, bladder and gastrointestinal tract; glands associated with G.I. tract, including liver and pancreas
What is involved in the transformation of trophoblast cells?
At the time of attachment, the some trophoblast cells fuse and become syncytiotrophoblast cells while the cells that don’t fuse are termed cytotrophoblasts.
What are some functions of the syncytiotrphoblasts?
Syncytiotrophoblasts are involved in perforating uterine vasculature and glands to eventually form the placenta. They also secrete human chorionic gonadotropin (HCG) which signals to the ovaries to keep producing estrogen and progesterone which maintains the uterine lining for pregnancy. Syncytiotrophoblasts are also involved in making decidual cells that form a distinct layer around the fetus to protect it from the immune system of the mother.
Where does chorion fluid come from?
Chorion fluid is produced from the trophoblast cells and is the fluid that surround the amnion and yolk sacs.
How does the neural plate form and from what cells does it arise from?
The neural plate is formed from the epiblast cells directly above the notochord. The notochord secretes the hormone sonic hedgehog to stimulate epiblast cell growth to form the thickened neural plate.
How does the neural tube form?
The neural plate begins to buckle and pucker into neural folds. These folds eventually fuse and form the neural tube.
What are neural crest cells and what do they become eventually?
Neural crest cells are the cells at the top of the neural folds and become detached from the lateral border of the folds and migrate within the embryo. The neural crest cells eventually become spinal and autonomic ganglia, Schwann cells, meninges, adrenal medulla, and melanocytes.
What is an epithelial-to-mesenchymal transition (EMT)?
This is the process by which differentiated epithelial cells become undifferentiated mesenchymal cells (“stem cells”) and is one way cancer can result.
What is are mesenchymal-to-epithelial transitions?
These are the transitions where undifferentiated cells become differentiated cells. This is typical in development.
What are some molecular tests used for DNA?
Southern blotting, restriction enzyme digestion, conventional sequencing, PCR
Go review these DNA tests..
:)
What are some molecular tests used for mRNA?
Q-RT-PCR, Northern blotting, microarray analysis
go review these mRNA tests…
super
What are some molecular tests used for protein?
ELISA, Western blotting
Please review these protein tests as well.
Nice
What are some emerging tests in the molecular biology field?
Deep sequencing – aka “next generation”
Therapeutic antibodies
Interference RNA (RNAi, microRNA, siRNA)
go review these tests too
What is regulative development?
Regulative development involves blastomeres that initially have similar developmental potencies each capable of giving rise to a complete embryo. Differentiation results from environmental signals which adjust to various perturbations.
What is mosaic development?
Mosaic development involves cell fate that has already been assigned during cleavage and a strict development plan is already in place; removal of one or more cells results in an incomplete embryo
What are the three methods of monozygotic twin development?
After the two-cell stage of development the embryo can:
- separate into two cells
- remain one cell with two separate inner cell masses
- remain one cell with a semi-divided inner cell mass – this can result in conjoined twins
Timing of splitting determines which path the embryo will take.
Totipotent
can give rise to all embryonic and extra-embryonic cell types and structures
Pluripotent
can give rise to all embryonic cell types and structures
Multipotent
can give rise to multiple (but not all) cell types
Unipotent
can give rise to just one cell type
induction
Induction involves the ability of one cell (or some type of environmental signal) to influence the development of another cell.
Cells not born different but are influenced during development by environmental signals regulative development
morphogens
chemicals/signals that alter cell fate
These are what cause induction to occur…
There are many different patterns for induction signaling. What are they?
- Inductive signaling – affects one other cell
- Gradient signaling – affects closest cell the most and tapers off as cells become farther away
- Antagonist signaling – cells receive an induced signal and an inhibitory signal which mix and affect the cells differently
- Cascade signaling – inductive signal affects the closest cell which then sends out another signal to the next closest cell, so on and so forth
- Combinatorial signaling – two inductive cells send signals to the close cells – mix of signals
- Lateral signaling – cells that are next to each other signal to one another
What determines whether a cell turns into a trophoblast or a cell in the inner cell mass?
This process involves Hippo signaling:
Outer cells: Yap expressed which associates with Tead4 and acts as a transcription factor for TE-specific genes such as Cdx2
Inner cells: Hippo expressed which phosphorylates Yap blocking it from entering the nucleus, thus TE-specific genes are not transcribed
What determines whether a cell will turn into an epiblast or a hypoblast?
The inner cell mass cells maintain Hippo signaling and express Oct4, Nanog, and Gata to maintain pluripotency.
Inner cells can only express either Oct 4 and Nanor OR Gata.
Gata-positive cells segregate out to form hypoblasts.
What is involved in the determination of the dorsal-ventral axis?
The mechanism is not well understood. However, an example is involved with neural tube development:
- Notochord induces ventral floor plate by secreting sonic hedgehog (Shh)
- Overlying ectoderm (former neural plate) induces the dorsal roof plate by secreting BMP
What is involved in the determination of the left-right axis in the body?
The left-right axis is determined by the direction of ciliary movement in the primitive node (flow counterclockwise by beating in same direction). This results in expression of Nodal on left side of the embryo and not the right side. Nodal then stimulates itself and another protein, Lefty, which inhibits nodal (mainly on the right side of body). Nodal stimulates production of Pitx2 which modulates gene expression patterns associated with l-r asymmetry such as heart development on the left.
Dynein mutations found to inhibit ciliary movement which affects l-r development.
What is involved in the determination of the anterior-posterior axis in the body?
Hox genes, which encode transcription factors that make homeodomains (DNA binding motifs) are involved in ant-post axis formation. Retinoic acid (RA) has been shown to regulate Hox expression and results in cell that have a more posterior fate.
What are the five major signaling pathways involved in morphogenesis and their basic features?
- TGF pathway (includes TGF and BMP proteins)
- neuronal differentiation, osteogenesis, LR asym - Hedgehog pathway (Sonic hedgehog - Shh)
- neural fate along DV axis, AP digit identity - FGF pathway (includes many FGFs)
- eye formation - Wnt pathway (involves APC – cell cycle)
- hematopoiesis, neural crest - Notch pathway
- hematopoiesis, neural development, somitogenesis
What morphogenesis pathways are associated with EMTs?
TGF-B, FGF, Wnt, and Notch pathways
What morphogenesis pathways are associated with METs?
BMP
What are the two types of cell migration?
Collective and single cell migration
How are cadherins involved in cell migration and adhesion?
- Selective cell-cell adhesion is mediated by cadherins that are expressed in tissue-specific patterns
- Cadherins of a certain type associate to one another
What is chemotaxis?
It is the characteristic movement or orientation of an organism or cell along a chemical concentration gradient either toward or away from the chemical stimulus – important in embryonic development
ex. sperm towards egg for fertilization; migration of neurons and lymphocytes
Affinity
very tight interaction at one small region; description of selectivity and strength of interaction
Avidity
several interactions that resemble a zipper or velcro; produces high binding strength, does not lead to refined selectivity
PAMP
(Pathogen associated molecular patterns) – outside
molecular moieties that are absolutely required for pathogen survival
ex. endotoxin (triggers production of IL-1), flaggelin, dsRNA, peptidoglycan, terminal mannose (cleaved by neuraminidase) –> sialic acid
DAMP
(Damage associated molecular patterns) – inside
recognized by innate immunity, sends out a danger/damage signal
ex. heat shock proteins; uric acid crystals, heparin sulfate, hyaluronan fragments
negative selection
T-cells that recognize self MHC molecules (and peptides) with high affinity are deleted from the repertoire of cells
Occurs when double positive T cells bind to bone-marrow derived APC (macrophages and dendritic cells) expressing Class I or Class II MHC plus self peptides with a high enough affinity to receive an apoptosis signal
Happens after positive selection. Involved in T cell education.
positive selection
The positive selection process leaves only T cells that can bind MHC molecules alive and are able to mature further
Occurs when double positive T cells bind cortical epithelial cells expressing Class I or Class II MHC plus self peptides with a high enough affinity to get the survival signal.
Happens before negative selection. Involved in T cell education.
MHC I
(major histocompatibility complex I) found on nearly every nucleated cell of the body; function is to display fragments of proteins from within the cell to T cells; healthy cells will be ignored, while cells containing foreign proteins will be attacked by the immune system
MHC II
(major histocompatibility complex II) MHC IIs are a family of receptor molecules normally found only on antigen-presenting cells and lymphocytes. The antigens presented by class II peptides are derived from extracellular proteins
CD1
clusters of differentiation – phenotypic protein markers on T cell membranes at different stages of differentiation in the thymus
CD1 is related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells
CD2 and 3 are retained at all times on peripheral T cells
Primary response for antibody production
Initially there is an increase in IgM response followed by and even greater IgG response
Secondary response for antibody production
After first infection, the response of IgM occurs but is lower than first insult, the total amount of antibody is drastically higher, and the amount of IgG is also greatly increased.
Dendritic cells
main function is to process antigen material and present it on the surface to other cells of the immune system; act as antigen-presenting cells
function as messengers between innate and adaptive immunity
Eosinophils
kill antibody-coated parasites through phagocytosis and extracellular degranulation
responds to allergies and helminthic parasites
Neutrophils
phagocytose targeted cells; have Fc and complement receptors; when cells die they form pus
CD4+ helper T cell
the T cell that reads the antigen and recruits the B cell to make antibody against it
CD8+ cytotoxic T cell
the T cell that attacks and kills the foreign element that has antibodies attached
Th0, Th1, Th2, Th17, and Treg cells
Th0, Th1, Th2, Th17 = T cells that differentiate in the thymus based on differences in the cytokines they secrete
Treg = T cells that can suppress other T cells and adaptive Treg cells that are active at the end of a normal immune response
Role of IFN gamma, TGF-B, IL4, and IL2 in antibody generation
- Th1 cells produce cytokines, such as interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor beta, and lymphotoxin
- Th2 cells secrete IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13
Complement
associated with a group of proteins that attach to a foreign element and portions of the C# proteins are cleaved forming anaphlatoxin (C3a, C4a, C5a) while the remainder of the protein is (C3b, C4b, etc) are attached to the foreign element and attract phagocytic vesicles to come and kill the foreign element
Somatic hypermutation
a cellular mechanism by which the immune system adapts to the new foreign elements that confront it
Mantoux test and delayed type hypersensitivity
The Mantoux test is a type IV delayed hypersensitivity reaction that involves injection of either purified protein derivative (PPD) or old tuberculin (OT). A positive test results when the memory Th1 cells produce cytokines that attract macrophages and cause induration (hardening of skin) and erythema (red swelling).
memory
property of adaptive immunity and produced by immunization; mechanism unknown
Innate immunity
is genetically hardwired, rapid response, limited repertoire; complement
Effector cells that:
- kill by contact = cytotoxic T cells, NK cells, and eosinophils
- phagocytosis = neutrophils, eosinophils, and macrophages
Adaptive immunity
acquired immunity creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen
B-cells make antibodies
Passive immunity
immunity that was given to a person such as already made antibodies
i.e. anti-venom, maternal, therapeutic monoclonal antibodies
Active immunity
introduction of an antigen that the body then makes antibodies against
i.e. vaccines, infection response
specific binding
used to label a molecule or cell for removal; criteria for both strength of interaction and selectivity
affinity vs. avidity
mast cells
release granules containing histamine, heparin, and TNF alpha – inflammatory response
