Lecture 5: Cleavage Flashcards
Post-fertilization events:
- Zygotes becomes metabolically active.
- Zygote begins to undergo cleavage (mitotic activity).
- Zygote is transported down uterine tube to uterus.
- This journey takes several days.
- Zygote loses zona pellucida prior to implantation.
- Implantation
Cleavage Events
• Zygotes undergoes mitotic division to form an 8-cell embryo.
• Cell division continues and compaction occurs:
• Occurs when outer blastomeres adhere via gap junctions and appear
to lose their individual identity.
• Involves E-cadherins and other calcium-dependent CAMs.
• Note that zona pellucida is still intact.
• Water is transported into the ball of cells (morula – 16 cells): • Occurs 4 days after fertilization
• Results in the formation of a blastocoel as a result of cavitation
• Requires Na and K-ATPase transporters
• Embryo is referred to as a blastocyst at this stage (58 cells).
Features of the Blastocyst
• Surrounded by zona pellucida
• Large, eccentrically placed blastocoel
• Consists of two types of cells: Outer layer of cells = TROPHOBLAST Inner mass of cells = INNER CELL MASS
Because of eccentric placement of blastocoel and inner cell mass, the blastocyst is polarized.
Because of eccentric placement of blastocoel and inner cell mass, the blastocyst is polarized.
- Embryonic pole marks the pole of the blastocyst where the inner cell mass is located.
- Abembryonic pole marks the opposite pole.
Forms extraembryonic structures including placenta.
Trophoblast, outer layer of cells
Forms embryo proper plus some Extraembryonic Structures.
Inner Cell Mass
In invertebrates and non-mammalian vertebrates:
Early control of cleavage is through gene products transcribed from the maternal genome and embryonic gene products often do not appear until after blastulation.
In mammalian embryos:
• Maternal gene products are produced but generally are
degraded by the 2-cell stage of development.
• By the four cell stage, most transcription is via the embryonic genome.
Methylation:
is the addition of methyl groups to specific regions of DNA molecules; it inactivates genes, including enhancers and promoters.
Methylation cycle:
- DNA of mature eggs and sperm is highly methylated.
- Demethylation of maternal and paternal genomes occurs shortly after fertilization until the early morula.
- Remethylation of inner cell mass occurs until late blastocyst state.
- Methylation levels fall after primordial germ cells enter genital ridges.
- Remethylation occurs later during gametogenesis and may lead to maternal/paternal imprinting.
Polarization of blastomeres at 8-16 cell stages
creates recognizable apical and basal surfaces.
Polarization of blastomeres determines
whether cells are destined to become part of the inner cell mass or part of the trophoblastic group of cells.
Two theories of polarization
- Inside-out hypothesis
* Cell polarity model
inside out hypothesis
• Fate of blastomere is determined by its position within the embryo, not from intrinsic properties.
Cell Polarity Model
- Cleavage plane parallel to the outer surface of the embryo: • Outer daughter cell → trophoblast cell (polar):
- Cells pick up a patch of outer cell membrane containing microvilli and ezrin (microfilament-stabilizing protein).
- Inner daughter cell → inner cell mass cell (apolar)
- Cleavage plane perpendicular to outer surface of the embryo:
- Both daughter cells become trophoblast cells.
potency
- Developmental potential = potency.
* Potency is greater than fate.
Genes involved in differentiation:
- Cdx-2:
- Essential for trophoblast cell differentiation
- Antagonistic toward
- Oct-4:
- Expressed in developing oocytes and zygote
- Required to permit cleavage to proceed to 2-cell stage
- Expressed in all morula cells
- May play a role in the maintenance of the undifferentiated state
• Nanog:
- Produced by inner cells in late morula stage stage
- Maintains integrity of inner cell mass along with oct-4
- Without Nanog inner cells differentiate into endoderm.
- Without oct-4 inner cells differentiate into trophoblast.
Sox-2
- First expressed in 8-cell stage
* Along with oct-4 it helps to control regulation of genes involved in differentiation.
Genomic imprinting
is differential gene expression depending on whether a chromosome is inherited from the male or the female parent.
It refers to the observation that expression of certain genes derived from the egg differs from the expression of the same genes derived from the sperm.
examples of genomic imprinting:
- Examples:Prader-Willi and Angelman syndromes.
* Due to DNA methylation differences in sperm and eggs
Parental Imprinting
• Occurs during gametogenesis
- Typically involves methylation of DNA
- Imprinted genes are maintained throughout development and perhaps adulthood.
- Note that imprinting is erased and reestablished with each round of gametogenesis.
Prader-Willi
Small hands and feet • Short stature • Poor sexual development • Mental retardation • Voracious appetites(usually obese) • Mutation is always inherited from father – (deletion in long arm of chromosome 15)
Angelman Syndrome
- Exhibit frequent laughter
- Uncontrolled muscle movement
- Largemouth
- Unusual seizures
- Mutation is always inherited from mother – (deletion in long arm of chromosome 15)
