Lecture 1 - Introduction to Cell Polarization

Question 1

Why is asymmetry of cell function so important?

Answer 1

Central to ability for complex activities

• cell - cell interactions
• directed transport & secretion
• DEVELOPMENT and MORPHOGENESIS

Question 2

How is polarization acheived?

Answer 2

- Asymmetry of signal transduction and gene/protein activity
- Cytoskeletal rearrangements
- Organelle biosynthesis
- Trafficking of membrane proteins and lipids

These factors adapt cell polarization to specific cell function.

Question 3

Epithelial cells are a good example of _____ asymmeteric organization

Answer 3

Stable

Question 4

Epithelial cells have an ___ and ___ surface domain. These are distinct _____ domains.

Answer 4

Apical; basolateral; surface

Question 5

What are the function of epithelial cells in the human body?

Answer 5

Tightly bound together to line major organs.

Liver, lung, intestine, kidney… YOU NAME IT

Question 6

Example of apical/basolateral morphologically different cells in the intestinal epithelia?

Answer 6

Microvilli - have finger-like extensions in the apical surface (caused by actin cytoskeletal structure).

Brush border have role in absorbing nutrients in final stages of digestion.

Question 7

What are the two roles of tight junctions in epithelial cells?

Answer 7

1. Barriers to movement of water, solutes, proteins
2. (Possibly, no strong literature evidence) Restrict movement of cell surface proteins and lipids across apical and basolateral domains

Question 8

Three events necessary of epithelia polarization?

Answer 8

1. Apical vs. basolateral domains need to form - in shape and composition
2. Junctions need to form (tight vs. adherens)
3. Receptorand lipids need to be asymmetrically moved to cell surface (A vs. B) and kept there

Question 9

What are neurites?

Answer 9

Unspecified extensions of neurons… one of which will differentiate to axons and the others into dendrites

Question 10

What are three ways axons and dendrites differ?

Answer 10

1. Shape
2. Molecular Composition
3. Function

Question 11

High gradients of BDNF and low gradients of semaphorin will lead to…

Answer 11

Axon differentiation

Question 12

High gradients of semaphorin and low gradients of BDNF will lead to…

Answer 12

Dendrite formation

Question 13

Why are axon and dendrite polarization in vitro studies different from in vivo studies?

Answer 13

In vitro– polarization does not have context; intrinsic signaling drives polarization.

In vivo - polarization is driven by external milieu; activation of intrinsic signaling by extrinsic factors is what polarizes cells

Question 14

Where do the dendrites form in the layers of the developing mammalian embryonic brain? Axons?

Answer 14

Dendrites - cortical plate
Axons - intermediate zone

The radial glial progenitor cells (which are like undifferentiated neural stem cells) originate in the ventricular sone and move up towards the subventricular zone. (from top to bottom CP-IZ-SVZ-VZ)

Question 15

Clicker Question:

Neuron are polarized cells that have two different compartments: axon and dendrite.

Gene A mediates axon formation. Gene B mediates dendrite formation. Is it possible both gene A and B are expressed in the axon?

A. Yes, given that an upstream activator of gene B is expressed exclusively in the axon but not in the dendrite.
B. Yes, given that an upstream activator of gene B is expressed exclusively in the dendrite but not in the axon.
C. Yes, given both genes are activated by the same extracellular cue which is present only in the extracellular space of the axon.
D. All of the above.

Answer 15

B.
Explanation: Cell signaling & polarization has hierarchy. If there is something regulating UPSTREAM of gene B specifying dendrites, and it is exlusive to dendrites, then only gene B will be activitated even if gene A is present.

Choice A is wrong because an activator of gene B (dendrite activator) upstream of gene B will trigger dendrite activation, not axon formation.

Choice C is wrong because if both genes are activated by the same cue (same ligand, same UPSTREAM activator), the cell cannot choose either dendrite formation or axon formation.

Question 16

Clicker Question

Gene A encodes and intracellular protein which mediates axon formation. BDNF is an upstream regulator of gene A. BDNF is a secreted extracellular factor. Gene A is not the cell-surface receptor for BDNF. Which of the following is correct:
A. BDNF is in the extracellular space of the axon.
B. Over-expression of BDNF is unlikely to rescue neuronal polarization upon deletion of gene A.
C. Over-expression of gene A will rescue neuronal polarization upon deletion of BDNF.
D. ALL of the above.

Answer 16

D. All of the above.
A. BDNF is a secred extracellular factor. It must be present in the EC environment of the axon for it to act on the axon (proximity = activation).
B. Upstream BDNF CANNOT rescue downstream gene A deletion (which is consistent with the choice)
C. Downstream gene A deletion CAN rescue neuronal polarization upon deletion of upstream BDNF).

Question 17

Clicker Question

Protein kinase A is important for axon development. Which is correct?
A. Deletion of PKA will result in formation of many axons.
B. Over-expression of PKA will result in formation of many axons.
C. Over-expression of PKA will result in many dendrites.
D. None of the above.

Answer 17

B. This one is stupid easy no explanation.

Question 18

Clicker Question

What are the advatanges of studying neuronal polarization in vitro vs. in vivo?

A. In vitro- allows examination and genetic manipulations of single cells (advantage)
In vivo- maintains the interactions of neurons with neighboring cells and tissues, thus allowing most reliable examination of neuron development (advantage)

B. In vitro models (disadvantage) disconnect neurons from their neighboring cells and from extracellular space.
In vitro models (disadvantage) - cells may die because they have been dissociated from their environment in the tissue.

C. In vitro models can give flase results because they have fundamentally different extracellular signaling properties than in vivo.

D. A and C are correct

E. A B C are correct.

Answer 18

E.
In vitro has the following advantages:
Allows single-cell examinations

In vivo has the following advantages:
1. Reliable signaling (maintains interactions of neurons with neighboring cells & tissue: external signaling is just as important as autonomous signaling

**In vitro has these disadvantages: **
Dissociating cells from their environment can cause different differentiation outcomes + ultimate cell death as they are no longer sustained by their neightboring cells and tissues