Donovan Flashcards
Expression from the embryo genome occurs when?
Late 1-cell early 2-cell stage
What is reductive cleavage?
Divisions with no increase in the embryo size
Potency of zygote to inner cell mass?
Zygote is totipotent
Inner cell mass is pluripotent
Inner cell mass becomes what?
Source of embryonic stem cells that eventually turns into the embryo proper
First cell differentiation in embryo?
Trophoblast
Describe the pre-implanted embryo
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
Describe implantation embryo
Invasion of uterine wall by trophoblast, evasion of immune response, establishment of blood supply between blastocyst embryo and uterus
Describe post-implantation embryo
Development of extraembryonic tissues predominate, gastrulation to form ectoderm, mesoderm, and endoderm of embryo proper
Describe maternal mRNAs role in development
Control early development through to the activation of the zygote genome
How is early genome controlled?
By imprinting to control the use of maternal or paternal derived genomes
T or F: Chromatin modifications are used in early embryo to control gene activity
T
Role of micro RNAs in early gene control
Extra regulatory mechanisms for gene activity
T or F: Retrotransposons and environment can impact development
T
What are common cell-cell interactions in development?
Cell adhesion, junction formation, signaling centers
What are morphogenic movements?
Migration of individual cells and Cooridinated movements of groups of cells
Cell growth and proliferation in development are indicated by?
increase in size and number of cells
Cell death in development?
Shape organ systems
Differential gene expression leads to?
Differentiation
What happens in fertilization on the embryo level?
Restoration of diploid, genetic variation, genetic sex determination, initiation of cleavage divisions as soon as membrane of egg is penetrated
Steps of fertilization
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
Two major cell types in early embryo
Trophectoderm - gives rise to trophoblast
Inner cell mass - embryo proper
Describe the loss of potency during development
Totipotent zygote
Pluripotent inner cell mass
Multipotent adult stem cells
Unipotent spermatogonia
What is compaction? What is the mechanism?
Developing blastomeres become compacted and tight junctions form between cells. E-cadherin increases and cells become polarized.
What are cadherins?
Mediate Ca+2 dependent cell cell adhesion. E-cadherin is needed for compaction
As the 8-cell compacts to the 16-cell morula what happens?
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
What is the trophectoderm?
First differentiated cells in embryo
What is the inner cell mass?
Pluripotent stem cells
Blastocyst leads to?
inner cell mass (pluripotent stem cells)
Trophoblast (outer, differentiated cells)
Inner cell mass leads to?
Epiblast (amnion embryo proper)
Hypoblast (yolk salk)
Trophoblast leads to?
Chorion (outer embryonic membrane)
Placenta (embryonic contribution to nutrient exchange)
Describe what happens in implantation to the embryo
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
Post-implantation of the embryo?
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
Chorionic sampling is used to?
Look at chromosomal disorder since it is derived from the fetus genome
What happens in gastrulation??
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
Describe migration in the primitive streak
Cells from the center of the epiblast migrate towards the hypoblast to form the endoderm and mesoderm
What is the ectoderm?
Outer suface of skin, CNS, and neural crest
What is the mesoderm?
Dorsal (notocord), paraxial (bone tissue), kidney, RBC, head, muscle basically
What is the endoderm?
Digestive tube, pharynx, respiratory tube
What are germ cells?
Egg and sperm
What is morphogenesis?
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
Describe neural tube formation
Notocord is important in formation from overlying ectoderm
Tube of ectoderm is formed in the mesoderm
notocord is equired for neural plate differentation
What signaling is required in neural tube formation?
Sonic hedgehog morphogen, bone morphogen protein to transform GF B family, paired box TF, slug TF
Sonic hedgehog does what in neural tube formation?
Induces the floor plate
Bone morphogen protein does what in neural tube formation?
Induces slug in the future neural crest
What are somites? Where are they located?
Mass of mesoderm that will eventually form the dermis, skeletal muscle, and vertebrae
Describe maternal mRA control of the early development
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
Describe the maternal to zygotic transition of genome
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
Describe regulation of the zygotic genome
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
What is chromatin?
Protein and DNA complex in nucleus
What is a nucleosome?
Fundamental repeating unit of chromatin with histones
Describe histone modification
Basic polypeptide tail extends from histone and can be modified
Acetylation of histone leads to?
Neutralization of histone charge and unravels
Methylation of histone leads to?
Silencing
What is genomic imprinting?
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
From sperm and oocyte to adult, development stages?
Zygote to morula to blastocyst to embryo
T or F: Genomic imprints are deleted and reestablished during gaetogenesis
T, can be affected by environment
The PcG protein repressive system is important for?
Pluripotent cell repression of genes that may be needed later in development, flexible repression
What happens to pluripotent-associated genes during differentiation?
Turned off via methylation
Describe modification of early germ-cell development
Turn off somatic genes via histone arginine methylation
DNA methylation does what besides on/off signals?
Allows parental origin to be identified
Describe global demethylation in germ cells
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)
Describe epigenetic modification at the Avy locus in mice
Hypomethylaton upstream of the promoter lead to yellow mice color. Pseudo-agouti mice are hypermethylated on these CpG islands
BPA in rats leads to?
Reduced methylation at certain loci and caused general hypomethylation
What is Prader-Willi syndrome?
Inheritance of deletion from the father, produces truncal obesity, small hands/feed, developmental delay
What is Angelman syndrome?
Deletion of mother imprinting on chromsome 15 leading to seizures, developmental delay, and characteristic gait
Earliest fate decision in developing embryo?
Development of the trophectoderm
What does OCT4 do?
Maintains pluripotentcy
What does CDX2 do?
Opposes OCT4 to dermine cells to become trophectoderm
What does the hippo signaling pathway do?
Regulates CDX2 transcription. Perhaps is regulated by cell contacts.
What is the first step of differentation?
Formation of the trophectoderm and the inner cell mass
Trophectoderm development is achieved by what signaling?
Upregulation of CDX2 and down-regulation of OCT4
What does the hippo pathway do?
Represses CDX2 expression on the inside cells to prevent differentiation to trophectoderm
GATA6 is positive in what cells?
Multipotent primative endoderm
NANOG positive cells are?
Pluripotent epiblast
Fusion of two germ cells makes?
Zygote, totipotent
Describe early germ cell development
Arise at one end of the epiblast (caudal end) and actively migrate from the gut tube to through the mesentary to developing gonads
First stage of gonad development
Specification, primordial germ cells become apparent at the caudal end of the primitive streak
What encourages primordial germ cell development?
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
What is BLIMP?
Active gene silencing in somatic genes of primordial germ cells
Second stage of gonad development
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.
What is cell substrate adhesion?
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
What is C-kit?
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
How is chemotaxis regulated?
SDF-1 binds to CXCR4 to transduce signal by increasing calcium levels and enhancing MAPK. Affects chemotaxis, proliferation, cell motility, and survival
What is meant by regulated apoptosis?
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
Stage 3 of gonad formation
Proliferation, apoptosis is regulated by proteins
Function of Bcl-2 family of proteins
Functions in germ cell as a survival pathway to block apoptosis
What is PTEN?
Inhibits signaling through AKT (increases cell survival)
Inactivation of PTEN leads to total survival and proliferation even if broken cell
Stage 4 of gonad development
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.
What is DAZL-RNA binding protein?
Essential for gametogenesis, central for spermatogenesis.
What is Stra8?
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
How do differentiated cells develop in gonad?
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
Are all 8 cells at the 8 cell stage totipotent?
Yes
8-cell to 16-cell is characterized most by?
Compaction
What is the blastocoel?
Space in the blastocyst
T or F: E-cadherin is needed for compaction
T
T or F: The embyro is recognized by the mother’s immune system
F
Why is the embryo not recognized by the mother’s immune system?
Produces factors encoded by paternal genes!
Amnion leads to development of?
Meso/ectoderm
Yolk sac develops to?
Meso/endoderm
Chorion develops to?
Mesoderm/trophoblast
The blastula develops into?
The gastrula
Gastrulation is characterized by?
Development of the mesoderm, ectoderm, and so on. Outer surface, CNS, Neural crest
What is the latest stage before implantation?
Blastocyst
What is IGF2?
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.
BPA in mice lead to what color?
Yellow, due to hypomethylation at Avy allele.
T or F: OCT-4 prevents inner cell mass from differentiating into trophectoderm
T
The epiblast is also known as?
The bilaminar disk
The SMAD pathway is activated by?
TGF-beta superfamily ligands
BMP binds to?
Type II receptors which phosphorylate Type I receptors. Type I receptors turn on SMAD via P. Ratio of SMAD4/SMAD6 determines signal strength
BMP4 binds to?
ALK2 receptor and activates SMAD
BMP4 leads to differentiation to what?
Primordial gonad cells
Blimp suppresses what?
Somatic genes
BMP signals what?
PGC genes
T or F: Blimp is expressed in both PGC precursors and PGCs?
T
KO of beta1 integrin leads to?
Defect in cell migration, undeveloped gonads (don’t migrate entirely)
C-kit activation among other things leads primarily to?
Cell survival (via AKT and BAD)
Spotting due to neural crest cell pigmentation issues can result from?
Mutations in C-kit receptors
CXCR4 is used by what virus?
HIV
SDF1 and CXCR4 lead to?
MAPK - proliferation/chemotaxis
PLC - Cell motility
PI3K - Survival
PGCs lacking SDF1 result in?
Failure to colonize genital ridge
Bcl-null animals results in?
Lesser gonad development/survival
PTEN inhibits?
AKT, tumor suppressor, inhibits PIP3 which decreases cell survival
Absence of PTEN leads to?
Activation of AKT leading to cell survival and proliferation of PGC
DAZL does what?
Takes PGC to meiosis competent germ cell
Low Retinoic acid leads meiosis competent germ cell to?
Go into G0 (male)
high retinoic acid along with STRA8 lead meiosis competent germ cell to?
Become meiotic germ cell (female)
