4-10 Flashcards

(94 cards)

1
Q

What is the hallmark event of the 8 cell stage in mouse embryo development?

A

Compaction - formation of adherens junctions that make intercellular boundaries obscure

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2
Q

What are E Cadherins essential for during embryo development?

A

Formation of adherens junctions during compaction

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3
Q

Where is E-cadherin localized during compaction?

A

Restricted to the basolateral cell–cell contact region.

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4
Q

What happens when embryos are exposed to anti-cadherin antibodies?

A

They fall apart due to disrupted cell adhesion

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5
Q

What happens to mutant embryos lacking E-cadherin?

A

They fall apart and die.

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6
Q

What type of binding do cadherins mediate?

A

Homophilic binding — cadherins on one cell bind to the same type on another.

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7
Q

What is the nature of individual cadherin–cadherin interactions?

A

Relatively weak, but collectively strong (like Velcro).

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8
Q

How do cadherins mediate adhesion between cells?

A

Through calcium-dependent homophilic binding between cadherins on adjacent cells; many weak bonds collectively create strong adhesion (like Velcro).

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9
Q

What are the main cadherin types and where are they found?

A

E-cadherin: epithelial cells
N-cadherin: nerve, muscle, lens
P-cadherin: placenta, epidermis

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10
Q

How do cadherins determine cell sorting and tissue organization?

A

Cells expressing the same cadherin stick together; higher cadherin levels create stronger adhesion — crucial for maintaining tissue architecture

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11
Q

Describe cadherin switching in neural development.

A

Ectoderm (E-cadherin) → Neural tube (N-cadherin) → Migrating neural crest (Cadherin-7). Correct switching is essential for proper migration.

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12
Q

Compare epithelial and mesenchymal cell features.

A

Epithelial: regular shape, polarity, strong adhesion, junctions, static
Mesenchymal: irregular, motile, front–back polarity, dynamic adhesions

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13
Q

What is EMT and why is it important?

A

Epithelial - Mesenchymal transition

reversible process where epithelial cells lose adhesion and gain motility; vital for development and cancer invasion.

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14
Q
A
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15
Q

How are cadherins involved in carcinoma progression?

A

Loss of E-cadherin weakens adhesion, allowing epithelial cells to invade through the basal lamina — a key step in malignancy.

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16
Q

How do tumor cells breach the basement membrane?

A

Via proteolytic ECM degradation by MMPs and serine proteases, enabling migration and invasion into surrounding tissue.

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17
Q

How is ECM degradation localized and regulated?

A

Proteases are secreted as inactive precursors, activated locally (e.g., by tissue plasminogen activator or uPA), and inhibited by TIMPs.

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18
Q

What are selectins and their function?

A

Carbohydrate-binding proteins on leukocytes and endothelial cells mediating transient, weak adhesion and rolling in blood vessels.

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19
Q

What is the function of integrins?

A

Mediate strong adhesion and emigration of cells, such as leukocytes entering tissues after rolling

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20
Q

Outline the leukocyte adhesion cascade.

A

Selectin-mediated rolling → Integrin activation → Firm adhesion → Transmigration into tissue

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21
Q

What are LAD-I, II, and III defects and their consequences?

A

LAD-I: ↓ integrins → defective firm adhesion/invasion
LAD-II: glycosylation defect in selectin ligands → defective rolling
LAD-III: integrin activation defect → defective adhesion & platelet issues

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22
Q

Summarize how cell adhesion affects development and pathology.

A

Cadherins organize tissues; selectins/integrins control immune migration; ECM remodeling enables cell movement — disruptions lead to developmental failure, inflammation defects, or cancer metastasis.

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23
Q

What are the main features of biological growth?

A

Anisotropy: Growth in unequal directions
Proportionality: Balanced body/organ scaling
Adaptability: Growth adjusts to environment (e.g., muscles enlarge, plants climb)
Discontinuous scaling: Organs scale with body, cell size stays constant

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24
Q

What factors limit how large a cell can grow?

A

Transport: Diffusion inefficiency in large cells
Communication: Difficulty coordinating signals across cell
mRNA synthesis: Finite transcriptional capacity limits protein production

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25
What strategies do cells use to grow large?
Vacuoles: Reduce active cytoplasm Syncytia: Multiple nuclei in one cytoplasm (e.g., muscle) Polytene chromosomes: Many chromosome copies (e.g., fly salivary glands) Helper cells: Transfer cytoplasm (e.g., oocyte support) Increased gene copies: Maintains DNA:cytoplasm ratio
26
How do most cells handle growth constraints?
They remain small but increase in number via cell division
27
What are the stages of the cell cycle and their main functions?
G1: Cell growth S: DNA synthesis G2: Growth + mitosis preparation M: Mitosis (cell division)
28
How do cyclins and Cdks control the cell cycle?
Cyclins bind and activate Cdks, forming active enzymes that phosphorylate target proteins. Each phase’s progression depends on the previous one’s completion.
29
When are specific cyclins active?
Cyclin D: G1 Cyclin E: S phase entry Cyclin A: S & G2 Cyclin B: Mitosis
30
What conditions must be met for G1 → S transition?
Adequate resources Enough space Presence of growth signals No “don’t divide” or DNA damage signals
31
How does Rb regulate the G1/S checkpoint and what is ATP’s role?
Rb (Retinoblastoma protein) blocks S-phase gene expression until phosphorylated by Cdks. Low ATP inhibits Cdk activity, preventing replication.
32
How do external signals influence cell cycle entry?
Growth factors activate Cyclin D–Cdk4/6. TGF-β and cell crowding activate p21, which inhibits Cdks. DNA damage induces p21 → Cdk inhibition → halted S-phase entry.
33
How do normal and cancer cells differ in growth signaling?
Normal cells: Rely on paracrine (cell-to-cell) signaling. Cancer cells: Often become autocrine, making their own growth factors or activating receptors abnormally.
34
How is cell cycle progression coordinated overall?
Cyclin–Cdk complexes drive progression → checkpoints ensure readiness → inhibitors (p21, Rb) halt cycle under stress → deregulation leads to uncontrolled division (cancer).
35
How does cell position affect growth in bacterial colonies?
Cells stay in place; outer cells receive more nutrients and divide faster. Growth on stiff agar is slower because movement is limited.
36
What are the three main orientations of cell division and their effects?
Periclinal: Increases tissue thickness (adds layers). Anticlinal: Increases circumference (surface area). Transverse: Increases length.
37
How does the schizorizA mutant differ in cell division from wild type plants?
Mutants undergo extra periclinal divisions, producing additional cell layers and extra girth before differentiating.
38
How does cell crowding or stretching affect proliferation?
Crowding: Inhibits division or causes cell death. Stretching: Activates Piezo1 Ca²⁺ channels, promoting division to relieve tension. Cells maintain homeostasis between crowding and stretch.
39
How does proliferation differ between the gut and mesentery?
Gut: High proliferation. Mesentery: Low proliferation but provides structural support. The gut loops because it grows faster than the mesentery allows.
40
What is Hertwig’s Rule and its significance?
Cells divide along their longest axis to reduce mechanical stress; division orientation adapts to substrate patterns and crowding cues.
41
What are the two main polarity types in epithelial cells
Apico-basal polarity: Vertical (z-axis), from basement membrane to apical surface. Planar cell polarity: Within the tissue plane (x–y axis), aligning cells across the sheet.
42
Which proteins define planar polarity and how are they distributed?
Frizzled (Fz): Localizes to the “North” side. Dishevelled (Dsh): Works with Fz. Stbm (Strabismus/Van Gogh) and Pk (Prickle): Localize to the “South” side. Together, they coordinate directional orientation across the tissue.
43
How is mitotic spindle orientation controlled?
Astral microtubules connect to cortical microtubule-binding proteins that “trap” or pull spindle poles, aligning the division axis.
44
What role does oriented mitosis play in neural tube development?
Divisions are oriented toward the tube’s edges, pushing the neural folds together for closure — failure of this can lead to neural tube defects.
45
How does the environment affect human growth?
Nutrition and disease levels strongly influence height; better nutrition and fewer diseases have increased average height over time.
46
What happens in fetal transfusion syndrome (in identical twins)?
Twins share a placenta; one twin receives more nutrient-rich blood, growing larger, while the other is undernourished and smaller.
47
What determines maximum body size in animals?
Species-specific genetic control — body size depends on which growth-regulating genes are active.
48
Why are females typically larger in many species, but not mammals?
Females often need greater nutrient reserves for reproduction; in mammals, hormonal regulation changes this pattern.
49
What is meant by proportionality in growth?
Body parts (e.g., arm span and height, or internal organs) grow in predictable proportions — represented by the Vitruvian “normal proportion” model.
50
Where is growth hormone (GH) produced and what does it control?
GH is secreted by the pituitary gland; it stimulates growth directly in muscles and indirectly in other tissues via IGF-I and IGF-II.
51
What are the effects of excess or insufficient growth hormone?
Too much: Gigantism (overgrowth, as in pituitary tumours). Too little: Dwarfism or stunted growth.
52
How do IGF-I and IGF-II regulate tissue growth?
GH acts on local tissues to induce IGF-I/II, which stimulate nearby cells to grow and divide — mediating overall body size.
53
How do bones grow in length?
Growth occurs at growth plates containing proliferating chondrocytes at the distal end; these mature, die, and calcify into bone
54
Describe the three main zones and their key signals in the growth plate.
Top: Proliferating chondrocytes (dividing; stimulated by PTHrP). Middle: Pre-hypertrophic cells (Indian Hedgehog triggers PTHrP). Bottom: Hypertrophic chondrocytes (mature; promoted by CNP and IGF-I).
55
How do Indian Hedgehog and PTHrP regulate bone growth?
Indian Hedgehog: Stimulates PTHrP → promotes proliferation. PTHrP: Maintains chondrocyte division and delays maturation
56
What are the roles of IGF-I and CNP in bone development?
IGF-I: Promotes bone formation and growth (from liver and local tissues). CNP: Encourages chondrocyte maturation (“mature!” signal).
57
What causes achondroplasia, and what are its effects
Activating mutation in FGFR3 — overactive FGF signalling inhibits chondrocyte proliferation and differentiation → premature growth plate closure → short limbs.
58
What does achondroplasia teach about body size regulation?
Growth plates and body parts respond independently to signals. Some body regions continue growing even when others stop — demonstrating localized control of growth and proportion.
59
How does skin maintain the correct surface area?
Skin grows in response to mechanical tension — stretching stimulates cell division, ensuring enough skin to cover the body (as seen in pregnancy or obesity).
60
What experiment tested mechanical tension in skin growth?
Cells grown with corners under high tension divided more rapidly, showing that mechanical stress promotes growth.
61
Why can organs move independently?
Organs are mechanically isolated — they grow and maintain size independently while the body can move without disturbing internal organ structures.
62
What did spleen transplantation in mice show about organ size control?
Multiple foetal spleens implanted in one mouse grew to fractions of normal size, together totaling one normal spleen’s mass → indicates systemic feedback control of total organ size.
63
How does the thymus differ from the spleen in growth regulation?
Multiple thymus grafts each grow to normal size, showing no feedback inhibition → indicates organ-specific control mechanisms.
64
What does the image with rounded corners show?
Mechanical stress is concentrated at sharp 90° corners and reduced in rounded corners — demonstrates how tissue geometry influences local cell division.
65
What is quorum sensing in multicellular tissues?
Cells secrete signalling molecules (factor X) that accumulate with population density; when concentration exceeds a threshold, it triggers coordinated responses like growth arrest or differentiation.
66
How does autocrine signalling contribute to quorum sensing?
Cells both secrete and detect factor X via their own receptors, allowing them to self-regulate once a collective threshold is reached.
67
How does kidney development show quorum sensing?
Weak Wnt4: mesenchymal cells remain loose. Strong Wnt4: cells aggregate and form epithelium. Wnt⁻/⁻ mutants can’t sense density → fail mesenchymal–epithelial transition. Li⁺ mimics Wnt, even without Wnt present
68
What role does feedback play in Wnt signalling and aggregation?
Positive feedback amplifies Wnt expression — once cells reach a critical density, Wnt reinforces its own production to drive differentiation.
69
What happens when autocrine signalling includes positive feedback?
Once the threshold of factor X is reached, feedback strengthens the signal, making the response irreversible — cells stop dividing and differentiate.
70
What is the trophic theory of neuronal survival?
Developing neurons depend on target-derived survival factors (neurotrophins); excess neurons die if they fail to receive enough trophic support.
71
What did altering chick limb targets reveal about neuron survival?
Removed limb: fewer neurons survive. Added extra limb: more neurons survive. → Neuron number is proportional to target tissue size
72
Name key neurotrophins involved in neuronal survival.
NGF (Nerve Growth Factor) BDNF (Brain-Derived Neurotrophic Factor) NT-3 (Neurotrophin-3) GDNF, CNTF, HGF
73
What determines whether a cell undergoes elective death?
Cells have a constitutive “death wish”. Survival factors (contact- or secretion-based) inhibit apoptosis. When deprived, cells die → maintains balance within and between tissues.
74
The fact that cells are different — they are specialised for distinct functions.
The process by which unspecialised cells become specialised, both in development and throughout life.
75
What is meant by “organs as communities of specialised cell types”?
Organs consist of multiple specialised cell types that perform different roles, creating a division of labour that allows the organ to function efficiently
76
Give an example of cell specialisation
Chromaffin cells in the adrenal gland synthesise the hormone epinephrine (adrenaline) using specialised enzymes unique to that cell type.
77
What are housekeeping and cell-type-specific proteins?
Housekeeping proteins: Found in most cells; essential for shared functions (e.g., metabolism, DNA repair). Cell-type-specific proteins: Present only in particular cells, enabling unique functions (e.g., epinephrine synthesis in chromaffin cells).
78
What does comparing proteins in different cell types show?
All cells share about 8,000 housekeeping proteins needed for basic functions, but each cell type also makes its own special proteins — about 3,500 in muscle cells and 4,000 in neurons — which give them their unique roles.
79
How do cells become different during development?
Cells begin identical but diverge through differentiation, guided by: Gene expression changes, and Cell signalling, which coordinates development across the embryo.
80
What are the key terms in embryonic differentiation?
Cell fate determination: The final cell identity. Cell lineage: The cell’s developmental origin. Lineage restriction: Limits on what a cell can become. Developmental potency: The range of fates a cell can adopt.
81
What are germ layers and why are they important?
Germ layers (ectoderm, mesoderm, endoderm) are key intermediate stages formed during gastrulation. Each layer gives rise to specific tissues and organs (e.g., ectoderm → nervous system, mesoderm → muscle, endoderm → gut).
82
How does mesoderm differentiation demonstrate progressive restriction?
Mesoderm cells: Express specific proteins and exhibit distinct behaviours (e.g., shape changes causing invagination). Have restricted potential, meaning they can form only certain tissues like muscle, bone, or kidney.
83
What is the main role of transcription factors?
Transcription factors are proteins that regulate gene transcription by binding to specific DNA sequences and switching genes on or off.
84
How does transcription begin in all protein-coding genes?
RNA polymerase II is guided to the promoter region by general transcription factors like TFIID, which binds to the TATA box — this sets the start point, not the timing, of transcription
85
What determines whether a gene is active in a cell?
1- The DNA binding sites in its enhancer regions. 2- Whether the matching transcription factors (TFs) are present in that cell.
86
What are enhancers and their function?
Enhancers are regulatory DNA sequences that bind specific transcription factors to activate or repress RNA polymerase, controlling when and where a gene is express
87
How do transcription factors work together to control gene expression?
Genes require combinations of transcription factors — for example, some TFs activate housekeeping genes, while others (like MyoD) activate cell-type-specific genes such as muscle proteins.
88
What are two ways transcription factors can influence chromatin?
Histone acetyl transferase (HAT): loosens DNA–histone interaction for easier access. Chromatin-remodelling complexes: reposition nucleosomes to allow RNA polymerase binding.
89
Describe how gene transcription differs between cell types.
All cells have the same genes, but different transcription factors determine which are active. Example: Red blood cells: TF1 + TF2 → β-globin gene ON. Muscle cells: TF1 + TF3 → myosin II gene ON.
90
What happens during muscle cell differentiation?
Mesodermal cells divide and lose growth factors. They exit the cell cycle, fuse together, and express muscle-specific proteins such as myosin II.
91
What is MyoD and its role in muscle differentiation?
MyoD is a muscle-specific transcription factor that binds to DNA at an E-box sequence (5’-CATATG-3’) as a dimer, turning on genes needed for muscle formation.
92
How does MyoD coordinate muscle development?
MyoD activates hundreds of target genes (e.g. myosin II, troponin, tropomyosin, creatine kinase), ensuring the coordinated expression of all proteins required for functional muscle cells.
93
What happens if MyoD target genes are knocked out?
Cells can still form muscle-like structures, but they will be non-functional, showing that MyoD’s targets are essential for muscle function, not initial differentiation.
94
How can cultured myoblasts be triggered to differentiate?
By removing growth factors from the culture media, myoblasts stop dividing, fuse, and express muscle-specific proteins (myosin II), mimicking in vivo muscle development.