01-16: Cleavage Flashcards
What are the 6 steps of cleavage in the Starfish?
Fertilized egg → First cleavage (2 cell stage) → Second cleavage (4 cell stage) → Third cleavage (8 cell stage = morula) → Early blastula → Late blastula
What are the 6 stages of cleavage in the Sea Urchin?
Fertilized egg → First cleavage (2 cell stage) → Second cleavage (4 cell stage) → Early morula → Late morula → Blastula
What does the unequal cleavage in the Sea Urchin result in?
Micromeres (small cells), Mesomeres (medium cells), Macromeres (large cells)
What happens to the zygote post-fertilization?
1- Becomes metabolically active 2- Begins to undergo cleavage 3- Transported down the uterine tube to the uterus (several days) 4- Loses ZP 5- Implantation
What are the steps of cleavage in humans?
Fertilized egg → First cleavage (2 cell stage) → Second cleavage (4 cell stage) → Morula (11 cell stage) → Blastocyst (Inner cell mass & Trophoblast) → Later Blastocyst
How does the blastomere adhere to each other so that compaction can occur?
gap junctions, E-cadherins, other Ca+ dependent CAMs
Is the ZP still intact during blastomere compaction?
YES because its still in the oviduct
How is the morula formed?
(4 days after fertilization) Na+/K-ATPase transporters draw water into ball of cells → forms morula (16 cells) → cavitation → forms blastocoel
What is a blastocyst surrounded by?
ZP
How does a blastocoel divide?
Eccentrically placed/pushed towards one pole → causes blastocyst to be polarized
When does blastomere polarization occur?
at the 8-16 cell stage
What does blastomere polarization do?
o Creates recognizable apical and basal surfaces
o Determines whether cells destined to become ICM (embryo) or Trophoblastic (placenta)
What are the 2 theories of Blastomere Polarity Establishment?
- Inside-out Hypothesis
- Cell polarity model
What determines the embryo polarity in the Inside-out hypothesis?
position of the blastomere within the embryo
NOT determined by intrinsic properties
What determines the embryo polarity in the cell polarity model?
plane of cell division during cleavage
What happens to the daughter cells if they divide PARALLEL to the cleavage plane?
- Outer daughter cell»_space; Trophoblast (POLAR)
- Inner daughter cell»_space; ICM (APOLAR)
What do the outer membrane cells of the outer daughter cells contain?
- microvilli
- ezrin (microfilament stabilizing protein)
What happens to the daughter cells if they divide PERPENDICULAR to the cleavage plane?
BOTH daughter cells»_space; Trophoblast (POLAR)
What is the Trophoblast and what does it form?
- Outer layer of Blastocyst
- Forms Extraembryonic structures (Placenta)
What is the Inner Cell Mass and what does it form?
-Inner mass of cells of Blastocyst
- Forms Embryo Proper
- Forms some Extraembryonic structures (yolk sac)
Where is the ICM located in the blastocyst?
at the embryonic pole of the blastocyst
Where is the Abembryonic pole located?
opposite to the embryonic pole/ICM
How is cleavage controlled in Invertebrate and Non-Mammalian Vertebrate Embryos?
Through gene products transcribed from maternal genome
When do the gene products transcribed from maternal genome appear?
after blastulation
How is cleavage controlled in Mammalian Embryos?
Through gene transcription mostly by the embryonic genome (4 cell stage)
Why is Mammalian Embryo cleavage controlled by embryonic genome instead of maternal genome?
maternal genome products are generally degraded by 2-cell stage
What is methylation?
addition of methyl groups to DNA molecules
What does methylation do?
Decreases DNA transcription which inactivates genes (such as enhancers and promoters)
When does Demethylation occur?
Shortly after fertilization»_space; Early Morula
maternal/paternal genome
When does Remethylation occur?
- Early Morula»_space; Late Blastocyst state (ICM)
- Gemetogenesis
What does Remethylation after gametogenesis lead to?
maternal/paternal imprinting
After primordial germ cells enter the genital ridges, what happens to the Methylation levels?
Methylation levels fall»_space; Causes the DNA to become more active
What has the max potency/potential?
zygote
What happens to the potency as the zygote development proceeds?
potency becomes more linear (more differentiated)
What are the 4 genes involved in differentiation?
- Cdx-2
- Oct-4
- Nanog
- Sox2
What is Cdx2 essential for?
trophoblast cell differentiation
What is Cdz2 antagonistic toward?
Oct-4
Where is Oct-4 expressed?
- in developing oocytes and zygote
- in all Morula cells
What gene is required to permit cleavage to proceed to the 2-cell stage?
Oct-4
Which gene may play a role in the maintenance of the undifferentiated state?
Oct-4
What produces Nanog genes?
inner cells in the late Morula stage
What does Nanog do?
maintains integrity of ICM along with Oct-4
What happens to the inner cells without Nanog?
inner cells differentiate into ECTODERM
What happens to the inner cells without Oct-4?
inner cells differentiate into TROPHOBLAST
When is Sox2 gene first expressed?
in 8-cell stage
What does Sox2 gene do?
Helps control regulation of genes involved in differentiation
What gene does Sox2 work with?
Oct-4
What is genomic imprinting?
differential gene expression depending on whether a chromosome is inherited from the male or the female parent
What are 2 examples of genomic imprinting?
- Prader-Willi (chromosome 15)
- Angelman syndromes
**Due to DNA methylation differences in sperm and eggs
When does parental imprinting occur?
during gametogenesis
What happens to the imprinted genes throughout the patient’s life?
they are maintained throughout development and perhaps adulthood
**permanent once they are an adult
When is imprinting erased and reestablished?
with each round of gametogeneis
What are the clinical manifestations of Prader-Willi?
- small hands and feet
- short stature
- poor sexual development
- mental retardation
- voracious appetites
Who is the mutation inherited from in Prader-Willi syndrome?
father
**Deletion in long arm of chromosome 15
What are the clinical manifestations of Angelman syndrome?
- exhibit frequent laughter
- uncontrolled muscle movement
- large mouth
- unusual seizures
Who is the mutation inherited from in Angelman syndrome?
mother
**Deletion in long arm of chromosome 15
When is methylation erased in mammals?
in germ cells of each generation
Why are there differential expression of male and female alleles in offspring?
because sperm and eggs undergo different levels of methylation
When does X inactivation take place in humans?
during first few weeks of development
What happens to the X chromosome after it is inactivated?
it remains inactivate in all descendants of the first cell
What causes X inactivation?
the action of Xist (X Inactivation Specific Transcript)
Where is Xist located?
on the X chromosome
What does Xist produce?
an RNA molecule that:
- Coats the X chromosome
- Induces X inactivation
What does coating the X chromosome with Xist RNA cause?
- Removal of acetyl groups from histone proteins
- Methylation of histones
- Alteration of histone composition
What region escapes X inactivation?
pseudoautosomal region
What is the Lyon Hypothesis?
the Barr body = inactive X chromosome
What is X-inactivation an example of?
- Dosage compensation
- Provides equal expression of X chromosome products in both males and females
Why is Lyon Hypothesis not seen in males?
because they only have 1 X-chromosome
** unless the male has 2 X-chromosomes
How many Barr Bodies can occur in Turner’s syndrome?
0 = XO
How many Barr Bodies can occur in Klinefleter’s syndrome?
1 = XXY 1 = XXYY 2 = XXXY 3 = XXXXY
How many Barr Bodies can occur in Triplo-X syndrome?
2 = XXX
How many Barr Bodies can occur in Poly-X females?
3 = XXXX 4 = XXXXX
How is X-inactivation involved in Tortiseshell cats?
Random inactivation of X chromosomes early in embryonic development produces a patchy distribute for the expression of X-linked characteristics
**Single X-linked locus determines orange color
What is the difference between imprinting and X-chromosome inactivation?
Imprinting = Autosomes
X-Chromosome inactivation = Sex Chromosomes
What is the ability of an embryo to compensate for removal of structures or for addition of structures?
regulation
What are some of the experimental methods of properties of early embros?
- Chimeras/Mosaics
- Fate mapping
- Totipotency
- Production of tetra/hexaparental embryos
- Production of interspecies chimeras
- Deletion or ablation experiments
- Addition experiments
- Transgenic embryos
- KO experiments
What is the procedure for producing tetraparental embryos?
Cleavage stages of 2 different strains of mice»_space; Removal of ZP»_space; Fusion of the 2 embryos»_space; Implantation of embryos into a foster mother»_space; Chimeric offspring obtained from the implanted embryos
What are types of twins?
- Fraternal (dizygotic)
- identical (monozygotic)
- Conjoined & Parasitic
What are the modes of Monozygotic twinning?
- Cleavage of an early embryo, with each half developing as a completely separate embryo
- Splitting of the ICM of a blastocyst and the formation of 2 embryos enclosed in a common trophoblast
- If ICM doesn’t completely separate, or if portions of the ICM secondarily rejoin, conjoined twins may result
What are the 5 types of conjoined twins?
- Cephalopagus (head to head)
- Pygopagus (rump to rump)
- Massive fusion of head and trunk
- Cephalothoracopagus (head and thorax)
- Thoracopagus (chest to chest)
