Donovan Flashcards

0
Q

Expression from the embryo genome occurs when?

A

Late 1-cell early 2-cell stage

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1
Q

What is reductive cleavage?

A

Divisions with no increase in the embryo size

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2
Q

Potency of zygote to inner cell mass?

A

Zygote is totipotent

Inner cell mass is pluripotent

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3
Q

Inner cell mass becomes what?

A

Source of embryonic stem cells that eventually turns into the embryo proper

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4
Q

First cell differentiation in embryo?

A

Trophoblast

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5
Q

Describe the pre-implanted embryo

A

Free floating in oviduct, surrounded by zona pellucida, divide without growth, expression of embryo genome occurs at late 1-cell, early 2-cell, reduction from totipotent zygote to pluripotent inner cell mass cells

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6
Q

Describe implantation embryo

A

Invasion of uterine wall by trophoblast, evasion of immune response, establishment of blood supply between blastocyst embryo and uterus

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7
Q

Describe post-implantation embryo

A

Development of extraembryonic tissues predominate, gastrulation to form ectoderm, mesoderm, and endoderm of embryo proper

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8
Q

Describe maternal mRNAs role in development

A

Control early development through to the activation of the zygote genome

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9
Q

How is early genome controlled?

A

By imprinting to control the use of maternal or paternal derived genomes

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10
Q

T or F: Chromatin modifications are used in early embryo to control gene activity

A

T

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11
Q

Role of micro RNAs in early gene control

A

Extra regulatory mechanisms for gene activity

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12
Q

T or F: Retrotransposons and environment can impact development

A

T

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13
Q

What are common cell-cell interactions in development?

A

Cell adhesion, junction formation, signaling centers

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14
Q

What are morphogenic movements?

A

Migration of individual cells and Cooridinated movements of groups of cells

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15
Q

Cell growth and proliferation in development are indicated by?

A

increase in size and number of cells

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16
Q

Cell death in development?

A

Shape organ systems

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17
Q

Differential gene expression leads to?

A

Differentiation

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18
Q

What happens in fertilization on the embryo level?

A

Restoration of diploid, genetic variation, genetic sex determination, initiation of cleavage divisions as soon as membrane of egg is penetrated

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19
Q

Steps of fertilization

A

Binding of sperm
Acrosome reacton to digest the corona radiata and zona pellucida
Sperm reaches egg membrane and fuses
Sperm block mechanism via electrical depolarization, Ca+2 influx causing cortical granules to fuse, zona pellucida swells and sperm receptors are inactivated

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20
Q

Two major cell types in early embryo

A

Trophectoderm - gives rise to trophoblast

Inner cell mass - embryo proper

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21
Q

Describe the loss of potency during development

A

Totipotent zygote
Pluripotent inner cell mass
Multipotent adult stem cells
Unipotent spermatogonia

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22
Q

What is compaction? What is the mechanism?

A

Developing blastomeres become compacted and tight junctions form between cells. E-cadherin increases and cells become polarized.

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23
Q

What are cadherins?

A

Mediate Ca+2 dependent cell cell adhesion. E-cadherin is needed for compaction

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24
Q

As the 8-cell compacts to the 16-cell morula what happens?

A

Creates an outer and inner environment which differs in contacts
Inner cells- contact other cells form gap junctions and becomes Inner cell mass
Outer cells - contact external environment and other cells. Form tight junctions and become the trophectoderm

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25
Q

What is the trophectoderm?

A

First differentiated cells in embryo

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26
Q

What is the inner cell mass?

A

Pluripotent stem cells

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27
Q

Blastocyst leads to?

A

inner cell mass (pluripotent stem cells)

Trophoblast (outer, differentiated cells)

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28
Q

Inner cell mass leads to?

A

Epiblast (amnion embryo proper)

Hypoblast (yolk salk)

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29
Q

Trophoblast leads to?

A

Chorion (outer embryonic membrane)

Placenta (embryonic contribution to nutrient exchange)

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30
Q

Describe what happens in implantation to the embryo

A

Blastocyst escapes from the zona pellucida
Trophoectoderm contacts and invades uterine epithelium (makes hCG)
Embryo develops into a bilaminar embryo (epiblast and hypoblast developed from inner cell mass) and trophoblast continues invasion

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31
Q

Post-implantation of the embryo?

A

Rapid growth and the external feature of embryo are formed
During most of 1st trimester is susceptible to environment/nutrition
Chorion develops around fetus and the chorionic villi create the interphase between the maternal and fetal circulation

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32
Q

Chorionic sampling is used to?

A

Look at chromosomal disorder since it is derived from the fetus genome

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33
Q

What happens in gastrulation??

A

Cell migration creates structures known as the gastrula from the blastocyst
Transforms the bilaminar disk into 3D embryo
Epiblast cells migrate toward the hypoblast
Migration of endodermal and mesodermal cells down the primative streak

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34
Q

Describe migration in the primitive streak

A

Cells from the center of the epiblast migrate towards the hypoblast to form the endoderm and mesoderm

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35
Q

What is the ectoderm?

A

Outer suface of skin, CNS, and neural crest

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36
Q

What is the mesoderm?

A

Dorsal (notocord), paraxial (bone tissue), kidney, RBC, head, muscle basically

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37
Q

What is the endoderm?

A

Digestive tube, pharynx, respiratory tube

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38
Q

What are germ cells?

A

Egg and sperm

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39
Q

What is morphogenesis?

A

Process of dynamic cell division and movement
Depends on direction and number of cell development, cell shape changes, cell movement, cell growth, cell death, and changes in the composition of cell membrane or secreted products

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40
Q

Describe neural tube formation

A

Notocord is important in formation from overlying ectoderm
Tube of ectoderm is formed in the mesoderm
notocord is equired for neural plate differentation

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41
Q

What signaling is required in neural tube formation?

A

Sonic hedgehog morphogen, bone morphogen protein to transform GF B family, paired box TF, slug TF

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42
Q

Sonic hedgehog does what in neural tube formation?

A

Induces the floor plate

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43
Q

Bone morphogen protein does what in neural tube formation?

A

Induces slug in the future neural crest

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44
Q

What are somites? Where are they located?

A

Mass of mesoderm that will eventually form the dermis, skeletal muscle, and vertebrae

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45
Q

Describe maternal mRA control of the early development

A

Early cleavage is controlled by maternal mRNA stored in the egg during oogenesis
Translation of mRNA is regulated by mechanisms that control polyAdenylation
Activation of the zygote genome doesnt occur until the 4 cell stage in humans
Maternal mRNA is degraded by the RISC complex in conjunction with miRNAs

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46
Q

Describe the maternal to zygotic transition of genome

A

Transcripts are accumulated in oogenesis (deadenylated)
Signals trigger recruitment of mask protein among others to polyadenylate the mRNA (after fertilization)
By gastrulation, all materal RNA is gone via miRNA, RISC, and Dicer

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47
Q

Describe regulation of the zygotic genome

A

Dynamic changes in expression occur during development leading to lineages
Activation/repression is controlled by the chromatin state
Changes in chromatin state by histone modification
Histone code instructs tx of specific genes

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48
Q

What is chromatin?

A

Protein and DNA complex in nucleus

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49
Q

What is a nucleosome?

A

Fundamental repeating unit of chromatin with histones

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50
Q

Describe histone modification

A

Basic polypeptide tail extends from histone and can be modified

51
Q

Acetylation of histone leads to?

A

Neutralization of histone charge and unravels

52
Q

Methylation of histone leads to?

A

Silencing

53
Q

What is genomic imprinting?

A

Epigenetic process by which certain genes are expressed in a parental specific manner. Involves methylation and histone modification. Imprinted alleles are silenced. Modifications are maintained in all cells of the body. Essential for development

54
Q

From sperm and oocyte to adult, development stages?

A

Zygote to morula to blastocyst to embryo

55
Q

T or F: Genomic imprints are deleted and reestablished during gaetogenesis

A

T, can be affected by environment

56
Q

The PcG protein repressive system is important for?

A

Pluripotent cell repression of genes that may be needed later in development, flexible repression

57
Q

What happens to pluripotent-associated genes during differentiation?

A

Turned off via methylation

58
Q

Describe modification of early germ-cell development

A

Turn off somatic genes via histone arginine methylation

59
Q

DNA methylation does what besides on/off signals?

A

Allows parental origin to be identified

60
Q

Describe global demethylation in germ cells

A

Important to reset the loci to be female/male depending on the contributing parent (e.g. female chromosome from male needs to be marked as coming from male)

61
Q

Describe epigenetic modification at the Avy locus in mice

A

Hypomethylaton upstream of the promoter lead to yellow mice color. Pseudo-agouti mice are hypermethylated on these CpG islands

62
Q

BPA in rats leads to?

A

Reduced methylation at certain loci and caused general hypomethylation

63
Q

What is Prader-Willi syndrome?

A

Inheritance of deletion from the father, produces truncal obesity, small hands/feed, developmental delay

64
Q

What is Angelman syndrome?

A

Deletion of mother imprinting on chromsome 15 leading to seizures, developmental delay, and characteristic gait

65
Q

Earliest fate decision in developing embryo?

A

Development of the trophectoderm

66
Q

What does OCT4 do?

A

Maintains pluripotentcy

67
Q

What does CDX2 do?

A

Opposes OCT4 to dermine cells to become trophectoderm

68
Q

What does the hippo signaling pathway do?

A

Regulates CDX2 transcription. Perhaps is regulated by cell contacts.

69
Q

What is the first step of differentation?

A

Formation of the trophectoderm and the inner cell mass

70
Q

Trophectoderm development is achieved by what signaling?

A

Upregulation of CDX2 and down-regulation of OCT4

71
Q

What does the hippo pathway do?

A

Represses CDX2 expression on the inside cells to prevent differentiation to trophectoderm

72
Q

GATA6 is positive in what cells?

A

Multipotent primative endoderm

73
Q

NANOG positive cells are?

A

Pluripotent epiblast

74
Q

Fusion of two germ cells makes?

A

Zygote, totipotent

75
Q

Describe early germ cell development

A

Arise at one end of the epiblast (caudal end) and actively migrate from the gut tube to through the mesentary to developing gonads

76
Q

First stage of gonad development

A

Specification, primordial germ cells become apparent at the caudal end of the primitive streak

77
Q

What encourages primordial germ cell development?

A

Bone morphogenic family of growth factors cause dimerization of receptors to phosphorylate SMAD, enters nucleus and activates target genes, may act in a paracrine fashion

78
Q

What is BLIMP?

A

Active gene silencing in somatic genes of primordial germ cells

79
Q

Second stage of gonad development

A

Migration, morphogenic movement from caudal epiblast to gut tube. Cells divide and grow, can push other cells away from reference point. This moves these germ cells to the hindgut.
Active migration up the hindgut mesentary towards the developing gonads.

80
Q

What is cell substrate adhesion?

A

In absence of adhesion, thee cell cant get traction and wont move. Integrin signaling can affect adhesion through the cytoskeleton through a cascade of P involving FAK

81
Q

What is C-kit?

A

Ligand is stem cell factor. Activates five different pathways, PI3K pathway leads to cell survival, adhesion, and proliferation.
SRC kinase, MAP kinase, and JAK/STAT pathways activated
IN ABSENCE, germ cell numbers are reduced

82
Q

How is chemotaxis regulated?

A

SDF-1 binds to CXCR4 to transduce signal by increasing calcium levels and enhancing MAPK. Affects chemotaxis, proliferation, cell motility, and survival

83
Q

What is meant by regulated apoptosis?

A

Germ cells must stay on path and get right signals. If go off path, lose signaling and undergo apoptosis
If they do not, they may go off course and turn back to pluripotent cells and form testicular tumors

84
Q

Stage 3 of gonad formation

A

Proliferation, apoptosis is regulated by proteins

85
Q

Function of Bcl-2 family of proteins

A

Functions in germ cell as a survival pathway to block apoptosis

86
Q

What is PTEN?

A

Inhibits signaling through AKT (increases cell survival)

Inactivation of PTEN leads to total survival and proliferation even if broken cell

87
Q

Stage 4 of gonad development

A

PGC arrive in gonad and proliferate to establish cell populations. Differentiate based on sex. Male germ cells enter mitotic arrest whereas females go into meiosis.

88
Q

What is DAZL-RNA binding protein?

A

Essential for gametogenesis, central for spermatogenesis.

89
Q

What is Stra8?

A

Required for transition into meiosis for both male and female germ cells. In F, required for pre-miotic DNA replication and subsequent events in meiotic prophase

90
Q

How do differentiated cells develop in gonad?

A

Early events in germ cell development are brought about by growth factor signaling
Repression of other programs needed for specification
Morphogenic movements of embryo bring to gonad
Germ cell numbers are regulated in space and time

91
Q

Are all 8 cells at the 8 cell stage totipotent?

A

Yes

92
Q

8-cell to 16-cell is characterized most by?

A

Compaction

93
Q

What is the blastocoel?

A

Space in the blastocyst

94
Q

T or F: E-cadherin is needed for compaction

A

T

95
Q

T or F: The embyro is recognized by the mother’s immune system

A

F

96
Q

Why is the embryo not recognized by the mother’s immune system?

A

Produces factors encoded by paternal genes!

97
Q

Amnion leads to development of?

A

Meso/ectoderm

98
Q

Yolk sac develops to?

A

Meso/endoderm

99
Q

Chorion develops to?

A

Mesoderm/trophoblast

100
Q

The blastula develops into?

A

The gastrula

101
Q

Gastrulation is characterized by?

A

Development of the mesoderm, ectoderm, and so on. Outer surface, CNS, Neural crest

102
Q

What is the latest stage before implantation?

A

Blastocyst

103
Q

What is IGF2?

A

Imprinted genes where mom’s is on and dad’s is off. Deleting mom’s leads to giants. Deleting dad’s leads to dwarfs. Deleting both is normal.

104
Q

BPA in mice lead to what color?

A

Yellow, due to hypomethylation at Avy allele.

105
Q

T or F: OCT-4 prevents inner cell mass from differentiating into trophectoderm

A

T

106
Q

The epiblast is also known as?

A

The bilaminar disk

107
Q

The SMAD pathway is activated by?

A

TGF-beta superfamily ligands

108
Q

BMP binds to?

A

Type II receptors which phosphorylate Type I receptors. Type I receptors turn on SMAD via P. Ratio of SMAD4/SMAD6 determines signal strength

109
Q

BMP4 binds to?

A

ALK2 receptor and activates SMAD

110
Q

BMP4 leads to differentiation to what?

A

Primordial gonad cells

111
Q

Blimp suppresses what?

A

Somatic genes

112
Q

BMP signals what?

A

PGC genes

113
Q

T or F: Blimp is expressed in both PGC precursors and PGCs?

A

T

114
Q

KO of beta1 integrin leads to?

A

Defect in cell migration, undeveloped gonads (don’t migrate entirely)

115
Q

C-kit activation among other things leads primarily to?

A

Cell survival (via AKT and BAD)

116
Q

Spotting due to neural crest cell pigmentation issues can result from?

A

Mutations in C-kit receptors

117
Q

CXCR4 is used by what virus?

A

HIV

118
Q

SDF1 and CXCR4 lead to?

A

MAPK - proliferation/chemotaxis
PLC - Cell motility
PI3K - Survival

119
Q

PGCs lacking SDF1 result in?

A

Failure to colonize genital ridge

120
Q

Bcl-null animals results in?

A

Lesser gonad development/survival

121
Q

PTEN inhibits?

A

AKT, tumor suppressor, inhibits PIP3 which decreases cell survival

122
Q

Absence of PTEN leads to?

A

Activation of AKT leading to cell survival and proliferation of PGC

123
Q

DAZL does what?

A

Takes PGC to meiosis competent germ cell

124
Q

Low Retinoic acid leads meiosis competent germ cell to?

A

Go into G0 (male)

125
Q

high retinoic acid along with STRA8 lead meiosis competent germ cell to?

A

Become meiotic germ cell (female)