Quiz 4 Flashcards
Embryonic Development Involves:
- Cell Proliferation
- Cell Differentiation
- Pattern formation and Morphogenesis
Cell Cycle
The sequence of stages through which a cell passes between one cell division and the next.
Cell cycle checkpoints Definition
Surveillance mechanisms that monitor the order, integrity, and fidelity of the major events of the cell cycle.
What are the Cell Cycle Checkpoints?
- G1/R checkpoint
- S-phase checkpoint
- G2 checkpoint
- Metaphase (M) checkpoint
G1/R checkpoint
Monitors external & internal conditions (DNA damage)
S, G2, & M checkpoints
Monitors internal conditions
During G1, cells are responsive to:
- nutrient levels
- anchorage dependance
- Mitogenic growth factors
- Anti-mitogenic TGF-beta signals
What are the choices prior to/ at R point?
- Remain in active proliferation.
- Exit from cell cycle (G0 or post-mitotic phase)
or - Apoptosis
What happens after passing the R point?
Cells commit to completing the cell cycle relatively independent of extracellular signals
What does evidence implicate about the deregulation of the G1/ R checkpoint?
the deregulation of the G1/r checkpoint is found in most if not all types of cancer cells
What happens before/during the G0 phase?
*Cells monitor internal and external conditions (signals) and make decisions about whether to continue proliferation or enter G0.
*Cells may may enter the G0 phase prior to the R checkpoint (G1 checkpoint) for a variety of reasons.
What are the three G0 states?
- Quiescent (resting, inactive)
- Senescent (not really resting or active)
- Differentiated (not active) — Terminally differentiated cells like nerve and muscle cells.
What G0 state is reversible?
Quiescent
Genes that regulate the cell cycle:
- are often mutated in cancer in two types of genes
What is the cell cycle clock?
A way to explain the molecular actions of many oncogenes and their effects on the clock ??
Proto-oncogenes
- Stimulates cell cycle progression
- Mutation in Cancer –> Gain of function mutation
-“Brake genes”
Tumor Suppressors
- Inhibits cell cycle progression
- Mutation in cancer –>Loss of function
- “Gas pedal genes”
How is genome integrity maintained?
Tumor suppressor p53 is activated in response to DNA damage
What is the p53 pathway responsible for?
- Halting the cell cycle until damage is repaired
- Initiating apoptosis
See Classic model of p53 activation
–
See the Classic model of p53 activation
–
p53’s function is sequestered by what?
MDM2
What are the sequential activation steps?
- Stress-induced stabilization of P53 mediated by phosphorylation
- DNA binding
- Recruitment of the general transcriptional machinery
Cell cycle molecular circuitry
Complexes of CYCLIN-DEPENDENT KINASES and CYCLINS regulate passage through checkpoints
-See figure-
How is progression through different checkpoints controlled?
Different cyclins rise and fall at different times during the cell cycle
What happens when a cyclin level reaches it’s threshold?
it binds to it’s cognate CDK
What are cyclins and CDKs regulated by?
Many different signals through signal transduction pathways
D1
Cyclin D1
Cyclin D1
Can be repressed to prevent cyclin CDK
What has been shown to possess a powerful anti-cancer effect?
Turmeric (Curcumin)
What two steps in embryonic development relate to stem cells?
- Cell Proliferation
- Cell differentiation
What are the two defining properties of stem cells?
- The ability to self-renew (self-regenerate, proliferate)
- The ability to differentiate into specialized stem cells
Differentiation
When an unspecialized early embryonic cell acquires the features of a specialized cell such as a heart, liver, or muscle cell
See the figure on cell differentiation steps
Draw Figure
Cell Potency
A cell’s ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater it’s potrncy
See the figure on the Hierarchy of Stem Cells
Draw Figure
Totipotent
- the state of a cell that is capable of giving rise to all types of cells found in an organism
- supports extra-embryonic structures of the placenta
- a single totipotent cell could reproduce the whole organism in utero
–Fertilized oocyte through 8 or 16- cell stage
Pluripotent
The state of a single cell that is capable of differentiating into all tissues of an organism, but not capable of sustaining full organism development
What is an example of Pluripotent?
Inner Cell Mass
Embryonic Stem Cell (ESC)
Primitive (undifferentiated cells derived from preimplantation-stage embryos) can divide without differentiating for a prolonged period in culture.
Known to develop into cells and tissues of the three primary germ layers
Multipotent
The ability to develop into more than one cell type of the body
Example of multipotent
Hematopoietic stem cells
What is an example of oligopotent and Unipotent?
Spermatogonial stem cells
Progenitor Cells
Divide a limited number of times and have the tendency to differentiate into specific cell types, usually unipotent, will differentiate into its “target” cell.
Which cell types have unlimited proliferation?
Zygotes
Embryonic stem cells
Multipotent stem cells
(see figure)
Which cells have limited proliferation?
Neuronal progenitor
Differentiating neuronal precursors
(see figure)
Which cells have no proliferation?
Differentiated cells
What happens as cells become more differentiated?
There is a loss of developmental potential. (POTENCY)
What do multipotent stem cells become?
Progenitor Cells
What is the typical course of embryogenesis?
It involves the specialization of stem cells into progenitor and precursor cells and then finally into adult tissue through differentiation or specialization.
Adult Stem Cells are also known as…
Somatic stem cells
Somatic stem cells
Their progeny replaces cells that are lost owing to tissue turnover or injury, thus ensuring the maintenance of tissue.
They are usually maintained in a quiescent state,and when activated, they proliferate to replenish damaged tissue
Cellular Plasticity
Describes the ability of some cells to take on the characteristics of other cells
Stem Cell Plasticity
- The ability of adult tissue-specific stem cells to switch to new identities.
- Stem Cell phenotypic potential (as opposed to normal cell fate)
De-differentiation
Cells go from a specialized function to a simpler state like stem cells
Trans-differentiation
The conversion of one differentiated (mature) cell type into another cell type (without undergoing an intermediate pluripotent state or progenitor cell type.)
Adult cell plasticity (in vivo)
retains the capacity to de-differentiate or transdifferentiate under physiological conditions, as part of an organ’s normal injury response.
Adult plasticity key points
-
Morphogenesis
- Creation of a well-ordered form
- Cell & tissue movement give the organisms or organs their 3D shape
- “Coordinated” with cell proliferation, differentiation, migration, cell death
- Tissues must be arranged in a precise pattern (pattern formation)
Pattern formation
Embryonic cells acquire identities that lead to a well-ordered spatial and temporal pattern of cell activities so that a spatially organized structure develops.
Body plan
Describes the overall organization of an organism. Involves defining the main axes of the embryo.
SEE AXES OF SYMMETRY FIGURES
What are the important Axes?
- Anterior — Posterior (Cranial — Caudal)
- Dorsal — Ventral
- Right — Left
Others:
- Medial — Lateral
- Proximal — Distal
What are the phases of pattern formation?
- Formation of body axes
-breaking symmetry - Organization of the embryo into smaller regions
- Segments develop specific characteristics
- Tissues & organs are produced
What are three stages in the embryonic period?
Cleavage
Gastrulation
Organogenesis
Gametogenesis
Formation of gametes
- Meiosis produces haploid cells (n) from diploid cells
What are the four phases of Gametogenesis?
- Extra embryonic origin of germ cells and their migration into the gonads
- Mitosis to increase # of germ cells
- Meiosis to reduce chromosome #
- Structural and functional maturation
SEE FIGURE FOR PHASE 1
- Gametogenesis
-
SEE FIGURE FOR PHASE 2 & 3
-Spermatogenesis & Oogenesis
-
In females Meiosis is not completed until….
Fertilization
Meiosis is _________ prior to fertilization, when depends on the species
Meiosis is _halted__ prior to fertilization, when depends on the species
What are the structural layers of the ovum?
Follicular cells of corona radiata
Cytoplasm
Nucleus
Zona Pellucida
What happens to the ovum prior to hatching and implantation?
The ovum is packed with material (maternal factors) for very early development. This allows for cleavage-stage development while the embryo travels down the oviduct
Fertilization accomplishes:
Fusion of male and female gametes to form a diploid zygote
Sexual reproduction
Egg/metabolic & initiation of development
Major Steps of Fertilization
-
Completion of egg meiosis Formation of pronuclei Mitosis begins…
Pronuclei fuse
Cleavage
Rapid cell division; little or no cell growth between divisions
Cleavage pattern
- Cleavage patterns vary among metazoans vary, but in each case, cleavage serves the same function.
-Cleavage produces a ball of cells with a fluid or yolk filled cavity — In deuterostomes
-By the completion of cleavage, cells take on different identities and symmetry is broken
Blastomere
a cell formed by cleavage of a fertilized ovum.
Blastocoel
The fluid-filled cavity of a blastula
Morula
a solid ball of cells resulting from division of a fertilized ovum, and from which a blastula is formed.
Blastula
Hollow ball of cells
-embryo
-blastocyst
What is the connection between cleavage pattern and early life?
Food source
Rate of cell division
Level of control by maternal genome
Food source
- Transition to free-living larva
- Yolk
- Placental attachment
Unless a large amount of yolk (food) is present in the egg, nutrients & metabolites will soon be exhausted and developing embryo/fetus will need an external food source
Maternal Control
Cellular processes carried out by transcripts/proteins present in the egg prior to fertilization
Allows for more rapid cell division; early zygotic control, slows cell division
Differences in cleavage patterns relate to different strategies for early development that depend partly on…
Yolk content
Cleavage pattern will determine:
- The relative sizes of blastomeres and their configuration
- Where and how cytoplasmic components are segregated into the different blastomeres
Emergence of pattern formation
Body Plan
Cleavage in Mammals
SEE FIG 2.2
-
Blastocyst
At the end of cleavage the embryo has entered the uterus and implants in the uterine wall, becoming a blastocyst
Inner cell mass —>
Embryo proper
-Embryonic stem cells
Trophoblast (outer cells)
Supporting structures contributes to placenta
Cell polarity model of differentiation of blastomeres….
May relate to the emergence of pattern formation
Gastrulation
Extensive rearrangement of cells
-Highly integrated cell and tissue movements in which the blastula is transformed into a three layered embryo with a primitive gut
Gastrula
Gastrulation-stage embryo
Gastrulation results in:
- Formation of the three germ layers
- Formation of the primitive gut (archenteron)
- “A tube-within-a-tube” body plan
- Elongated rostrocaudal axis
Blastopore
Opening to the primitive git becomes the anus in vertebrates and echinoderms
Germ Layers
- Ectoderm
- Mesoderm
- Endoderm
Epithelial cells
Strong interactions other cells (cell adhesion) and ECM; stationary, polar
-See figure
Mesenchymal cells
Weak/no interactions with other cells or ECM; mobile (can migrate and invade), no cell polarity
See figure
Ectoderm
- The outermost layer of the gastrula
- Nervous and sensory systems, epidermis
Mesoderm
- Partly fills the space the space between the ectoderm and endoderm
- Skeletal, muscular, and circulatory systems, excretory and reproductive systems, dermis; notochord
Endoderm
- Lines the achentron
- epithelial lining of the digestive tract and associated organs
Epithelial lining of the respiratory system (lungs)
See figures on Gastrulation
Organogenesis
The organs of the animal body form from the three embryonic layers
What is the order of a tube within a tube body plan?
outer most – Ectoderm – mesoderm – endoderm – innermost
Cell Differentiation
Cells interact with each other and acquire different identities
Morphogenesis
- Segments form and develop specific characteristics
- Organized spatial patterns of differentiated cells, tissues folding or splitting
- Formation of tissues and organs
Notochord
Embryonic “backbone” (not present in adult mammals)
Source of inducing signaling
Somites
Somites give rise to the cells that form the vertebrae and ribs, the dermis of the dorsal skin, the skeletal muscles of the back, and the skeletal muscles of the body wall and limbs.
Neurulation
- Formation of the neural tube
- Along with notochord, 1st organ-like structures to form
From ectoderm, neurulation produces:
- Epidermis – epidermis, eye lens, anterior pituitary
- Neural tube – central nervous system (brain, spinal cord), retina
- Neural Crest – peripheral nervous system, facial cartilage
Cell shape changes
cell shape changes by apical constriction
coordinated changes in cell shape can cause cell layers to buckle, roll, extend, and/or shrink
Epithelial-to-Mesenchymal cell transitions (EMT)
- require a loss of cell adhesion
- are important for development, but also a hallmark of cancer
during differentiation, different types of cells form with different adhesion, allowing them to specifically adhere to each other and form tissues
Cadherins
- Calcium-dependent cell adhesion proteins
- Homotypic binding specificity
-Involved in many morpho-regulatory processes including the establishment of tissue boundaries, tissue rearrangement, cell differentiation, and metastasis
Intercalation
Cells mover in between adjacent cells
invagination
the infolding of sheet cells, much like the indenting of a hollow rubber ball when poked
Involution
a type of cell movement during gastrulation that involves the interning or inward movement of an expanding outer layer so that it spreads over the internal surface of the remaining external cells.
ingression
the migration of individual cells from surface layers into the interior of the embryo
Epiboly
“over the ball” – usually the growth of epidermal ectoderm to cover the surface of the embryo during gastrulation
Delamination
splitting of one cellular sheet or layer into two parallel layer
convergent extension
elongation of a cell layer in one dimension and shortening in another dimension
Neurulation
Notochord forms and secretes signals that induce formation of the neural tube
Cell shape changes
produce hinge points for rolling up of the neural tube
What dorsalizing signals from the notochord simulate neural function
Chordin and noggin
Cell adhesion changes
Neural crest cells and separation of neural tube from epidermis
Neurulation results in
the differentiation of ectoderm into 3 types of lineages
Neurelation steps
Early cleavage cells —> Inner cell Mass —> ectoderm —>neural tube —> forebrain “segment” —> cerebrum
Homeodomain-containing TFs
Hox
Pax
Lim
Homeodomain
60 amino acids in length
Hox transcription factors
- Hox TFs pattern the anterior-posterior body axis playing a crucial role in segment-specific organogenesis
- ## Normal temporo-spatial limb and organ development
Pax transcription factors
Involved in pattern development / regional specification
LIM transcription factors
Involvement in tissue patterning and differentiation, particularly neural patterning
MyoD
Master Regulator — turns developing cells into muscle cells
Zinc finger transcription factors
- Sox
- WT1
- Kruppel
Sox
Helps differentiate germ layers
