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Early Development Flashcards

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1
Q

What are the four types of amniote vertebrates?

A

Reptiles, birds, monotremes, and placental mammals.

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2
Q

What are the characteristic structures of the amniote egg?

A

Chorion, contains blood vessels for gas exchange.
Amnion, enables embryo to float in a fluid environment.
Yolk sac, enables nutrient uptake and development of circulatory system.
Allantois, stores waste at the embryonic posterior.
Placenta in mammals, joins uterus and allows nutrient/gas exchange and waste elimination.

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3
Q

Why is the chicken a model organism?

A

Accessible and easily maintained.
Stable, universal development.
Organ formation is genetically similar to mammals.
Can be surgically and genetically manipulated.

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4
Q

What are the smallest eggs in the animal kingdom?

A

Mammalian eggs.

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5
Q

What is mammalian development classified as (oviparous, viviparous, ovoviviparous)?

A

Viviparous.

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6
Q

When does cleavage of an embryo begin? And where in the uterus?

A

Meiosis is completed as soon as the sperm enters the egg. The first cleavage begins about a day later. The cilia in the oviduct push the embryo towards the uterus, and the first few cleavages occur along the way.

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7
Q

What factor is required to initiate the first cell division in mice?

A

A sperm-borne miRNA-34-c.

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8
Q

When does the blastocyst hatch from the zona? What are the outcomes?

A

After days 5-6, the blastocyst hatches from the zona, allowing implantation.

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9
Q

What type of cleavage do human eggs undergo? Describe it briefly.

A

Holoblastic rotational cleavage whereby the cleavage plane rotates 90° after the first division.

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10
Q

What is the rate of human egg cleavage?

A

Since cleavage is asynchronous, different blastomeres divide at different rates. No exponential cleavage occurs, and an odd number of cells is common.

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11
Q

How are zygotic genes activated? When does this occur, and what is the outcome?

A

New histones are placed on the DNA during early cell division, and DNA is completely demethylated, except for imprinted genes. The outcome is a totipotent stem cell around the 4-16 cell stage.

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12
Q

Why do human zygotic genes need to be activated so early?

A

Mammalian eggs do not have maternal factors, thus necessitating embryonic gene expression.

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13
Q

Why, when, and how does the blastomere become compact?

A

At the 8-cell stage, the cells clump tightly via gap junctions and E-cadherins to segregate the inner cells from the outer cells. This separates the ICM embryo proper cells from the OCM trophoblast cells.

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14
Q

What is the first differentiation event in mammalian development? Describe it briefly.

A

The OCM differentiating into the chorion, or the embryonic portion of the placenta. These trophoblast cells adhere to the uterine lining then digest a path for implantation in the wall.

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15
Q

How does embryonic cavitation occur, and what is the outcome?

A

When the morula enters the uterus, fluid breaches the zona, entering the ICM environment. This forms the blastocoel, which is the hallmark of cleavage.

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16
Q

What factors are associated with pre-blastocyst cells, ICM cells, and OCM cells?

A

Pre-blastocyst: All cells express Cdx2 and Oct4.
ICM: No Cdx2, High Oct4, Sox2, Stat3.
OCM: High Cdx2, inhibits Oct4.

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17
Q

How is Nanog involved in ICM/OCM determination?

A

Oct4 induces the expression of Sox2. The presence of Sox2 in the ICM upregulates Nanog, thus resulting in a feed-forward mechanism. This response exponentially increases the concentration of Sox2, Oct4, and Nanog.
In the trophoblast, Cdx2 inhibits Oct4, and thus Sox2 and Nanog are not expressed.

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18
Q

How does the initial trophoblast attachment occur?

A

At day 6, the trophoblast of the embryonic pole penetrates the uterine mucosa. L-selectins of the trophoblast cells bind to carbohydrate receptors of the uterine mucosal wall. Several cell adhesion molecules are then expressed, including integrins, laminin, and fibronectin.

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19
Q

How does the embryo completely implant into the uterine wall?

A

When in contact with the endometrium, Wnt instructs trophoblasts to secrete proteases, thus digesting the uterine ECM for embryonic burial.

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20
Q

What key events happen during the first week of development?

A

Fertilization, cleavage, compaction, first differentiation, and early implantation.

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21
Q

What key events happen during the second week of development?

A

Completion of implantation, bilaminar germ disc formation, and chorionic cavitation.

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22
Q

What is the hallmark of the second week of development?

A

Bilaminar germ disc cleavage and full uterine implantation.

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23
Q

What does the trophoblast differentiate into during the second week?

A

An inner mononucleated cytotrophoblast, and an outer multinucleated syncytiotrophoblast.

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24
Q

What does the embryo proper differentiate into during the second week?

A

The epiblast, adjacent to the amniotic cavity, and the hypoblast, adjacent to the yolk sac.

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25
T/F: The hypoblast contributes to both the embryonic and extraembryonic structures.
False, only extraembryonic.
26
What factors do the epiblast and hypoblast express?
The epiblast expressed Nanog whereas the hypoblast expressed Gata6.
27
What are amnioblasts?
Cells of the epiblast adjacent to the cytotrophoblast.
28
Where is the amniotic cavity formed?
Between the amnioblast and the underlying epiblast cells.
29
What is the lacunar stage of embryonic development?
As the syncytiotrophoblast expands into the highly vascularized endometrial stroma, its multinucleated cytoplasm develops small vacuoles that fuse into lacunae. The maternal vasculature then opens into lacunae, bathing the embryo in nutrients and gases.
30
What is the connecting stalk? What is its fate?
The connecting stalk attaches the germ disc to the trophoblast by the connecting stalk inside the extraembryonic or chorionic cavity. It later differentiates into the umbilical cord.
31
What is the exocoelomic membrane?
Derived entirely from hypoblast cells, lines the exocoelomic cavity, or primitive yolk sac.
32
What is the extraembryonic mesoderm?
Forms between the exocoelomic cavity cells and the cytotrophoblast cells, later expanding to form the extraembryonic cavity, or chorionic cavity.
33
What are the hallmarks of the third week of development?
Gastrulation, trilaminar germ disc formation, and body axis determination.
34
What did Spemann & Mangold discover?
When splitting the embryo, the lack of a primitive streak in the divided cells disrupts development and forms a "belly piece" whereas the presence of a primitive streak leads to normal development. This bolsters the role of the primitive streak as a developmental organizer and supports the notion of nuclear equivalence.
35
When and how does the primitive streak form?
At the caudal end, a primitive streak of epiblast cells mark the future midline. These cells apically constrict to form a primitive groove, and the anterior-most portion becomes the primitive node, which is the body's organizer.
36
Where does the primitive streak extend, and where does it regress?
It extends from caudal to rostral and regresses from rostral to caudal.
37
What happens at the primitive groove?
Cells undergo EMT to gastrulate, with the first cells reaching the deepest portion to become the endoderm. The cells that get wedged between the endoderm and epiblast become the mesoderm, and the remaining epiblast cells become the ectoderm.
38
When does the primitive streak disappear?
After the mesoderm is formed.
39
What is the Nieuwkoop center of amphibians?
Formed by the dorsal translocation of Disheveled and Wnt11, stabilizing the beta-catenin by complexing it with Tcf-3 to activate Siamois and Twin. These two factors interact with the Smad2 factor activated by vegetal Tgf-beta to further activate the organizer genes goosecoid, chordin, and noggin.
40
What is the posterior marginal zone?
The avian equivalent of the amphibians' Nieuwkoop center.
41
T/F: Germ layer identity is established during gastrulation.
False, before gastrulation.
42
How is cell migration during gastrulation controlled?
By FGF8, which is synthesized by the streak cells themselves. FGF8 downregulates E-cadherin in the presumptive EMT-exhibiting cells.
43
What is the prechordal plate?
Also known as the prenotochordal plate, it forms in the lateral mesodermal-endodermal plane between the notochord and a lateral-most pinching of ectoderm-endoderm called the oropharyngeal membrane at the rostral end of the embryo.
44
What are the oropharyngeal and cloacal membranes?
Ectoderm-endoderm bilayers formed at the rostralmost and caudalmost portions of the embryo, respectively.
45
How is the notochord formed?
When cells invaginate through the primitive node, some get intercalated within the hypoblast to form the notochordal plate. As the hypoblast portion is replaced, the definitive notochord is formed.
46
What is the anterior visceral endoderm?
The AVE is the mammalian equivalent of an early anterior-organizer: a small, migratory patch of visceral-endoderm cells that migrates to the future “front” of the embryo, secreting Cerberus and Lefty to inhibit Nodal and determine the head–tail axis before gastrulation even begins.
47
What are the factors Cerberus and Lefty with respect to Nodal?
Cerberus and Lefty are head-inducing and posterior-inhibiting factors whereas Nodal is a posterior inducer.
48
What happens if the anterior visceral endoderm does not form?
No cephalization occurs, and the embryo no longer develops.
49
What is HNF-3beta?
It maintains the primitive node and later specifies the forebrain and midbrain structures.
50
What happens if HNF-3beta is under-expressed? What if it was over-expressed? And knocked-out?
Under-expressed: Developmental failure. Over-expressed: Multiple nodes or conjoined twins. Missing: No node, no gastrulation, and no forebrain and midbrain.
51
How is the mesoderm ventralized? What does this mean?
In the presence of BMP4 and FGF. This portion of the mesoderm forms the kidneys, blood, and body wall.
52
What are the BMP4 antagonists? In what context are these factors employed?
During establishment of the body axis, Chordin, Noggin, and Follistatin antagonize BMP4 which normally ventralizes the mesoderm. As a result, the cranial mesoderm is dorsalized into the notochord, somites, and somitomeres.
53
What differences are observed between the anterior and posterior embryonic cells?
Anterior: Nodal, BMPs, Wnts, FGFs, and RA. Posterior: BMP and Wnt antagonists.
54
What factor is deployed in a gradient along the posterior axis? How is this gradient formed?
FGF8, and its gradient is formed by the decay of FGF8 mRNA in newly formed posterior tissues, retaining it in the posterior tip.
55
During axis formation, where is retinoic acid found?
At the dorsal, ventral, and posterior poles of the embryo. It is degraded at the anterior.
56
How many copies of Hox genes do mammals have?
Four copies per haploid set, located on four different chromosomes.
57
What factor activates the Hox genes? At which pole of the embryo?
Cdx, at the posterior pole.
58
What are Hoxa3, Hoxb3, Hoxc3, and Hoxd3 called?
Paralogues.
59
In what order are the Hox genes expressed?
Backwards, from Hox13 to Hox1.
60
If the order of Hox genes respectively transcribes coccygeal, sacral, lumbar, thoracic, and cervical portions, what would the knock-out of the sacral region cause?
Extension of the lumbar region.
61
Why are organ systems asymmetric? Specifically, why is the right lung composed of three lobes compared to the left lung's two lobes?
Determination of the L/R axis induces changes in organ systems. For instance, FGF8 secretion in the left side of the embryo may cause the asymmetry in lung lobes.
62
What is Pitx2 and what factors are associated with it?
FGF8 maintains Nodal expression in the lateral plate mesoderm, as well as Lefty-2, and both these factors upregulate Pitx2. It establishes left-sidedness.
63
What is the Brachyury gene?
Encodes notochordal transcription factors and is essential in the expression of Lefty-1 and Lefty-2.
64
How is serotonin involved in axis formation?
Also called 5-hydroxytryptamine or 5HT, serotonin is concentrated on the left side and is upstream from FGF8 signaling.
65
What are the disorders associated with serotonin in axis formation?
Situs inversus, dextrocardia, [...]
66
How is Shh involved in axis formation?
Represses left-sided gene expression on the right.
67
Where is Cerberus expressed, and what does it do?
At the anterior right, inhibiting Nodal.

BIO401 (3 decks)

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