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BI320: Molecular Genetics

How is cell fate determined?

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Cell Fate: The Big Picture


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Objectives
Mechanisms

Each multicellular organism was once


a single cell.

Knowledge Check
Scientific Method
Scenario
Summary

Video goes here

How do dierent cells in a multicellular


organism end up expressing dierent genes?

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Each time a cell divides it distributes identical


copies of its DNA to its two daughters and also
splits its cytoplasm roughly evenly between
them. How can the daughters end up expressing
dierent genes? We previously learned that there
are three dierent mechanisms that allow cells to
do this.

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Cell Fate: Objectives


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Introduction
Mechanisms
Knowledge Check

By the end of this lesson, you will


be able to:

Scientific Method
Scenario

1.

Formulate a
hypothesis

2.

Propose an
experiment to test
the hypothesis

3.

Interpret
results of the
experiment

Summary

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Cell Fate: Mechanisms (part 1)


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Introduction
Objectives

How can daughter cells


end up expressing
dierent genes?

By chance
Asymmetric cell division
Cell-cell signaling

Knowledge Check
Scientific Method
Scenario
Summary

By chance:
The two daughters will inherit identical DNA. But it is unlikely that
they will receive EXACTLY the same number of molecules of a
particular mRNA or protein even if they are randomly distributed
within the mother cell's cytoplasm.
For example, if there are only a few molecules of an
important protein X in mom - say 3 - then inevitably one
daughter will receive at least twice as much protein X as
the other.
We already learned that this initial
dierence can then be amplied by
feedback. If protein X regulates gene
expression then the two daughters will
end up expressing dierent genes.

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Cell Fate: Mechanisms (part 2)


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Introduction
Objectives
Knowledge Check
Scientific Method
Scenario
Summary

Asymmetric cell division:


One or more proteins or mRNAs are already
asymmetrically distributed within the mother cell's
cytoplasm so that when the mother cell divides, the
cytoplasms that the two daughters inherit are
dierent.
For example, if protein X is located on the
"left" side of the mother cell, which then
divides into a "left" daughter and a "right"
daughter, then the left daughter will receive
protein X and the right daughter will receive
none.
Again, if protein X regulates gene
expression then the two
daughters will end up expressing
dierent genes.

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Cell Fate: Mechanisms (part 3)


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Introduction
Objectives
Knowledge Check
Scientific Method
Scenario
Summary

Cell-cell signaling:
Either the mother cell receives an asymmetrical signal
from an adjacent cell or only one of the daughter cells
receives a signal from an adjacent cell. A signal to the
mother cell can cause her to localize specic mRNAs
or proteins asymmetrically within her cytoplasm -
placing them either near or away from the source of
the signal.
If she then divides asymmetrically then her
daughters will be dierent (see mechanism 2).
A signal to only one of the daughter cells can
cause it to change the genes it expresses. The
other daughter, having not received the signal,
will not make these changes in the genes it
expresses.

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Cell Fate: Knowledge Check (part 1)


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Introduction
Objectives
Mechanisms

You observe the


following pattern
of cell division:

Scientific Method
Scenario
Summary

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What mechanism(s) might cause daughter cells C & D


to express dierent genes?
a. The dierence arose by chance.
b. Cell A was already asymmetric (because its mother was
asymmetric) and then divided asymmetrically.
c. Cell B signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
d. Cell B signaled to C only, causing it to repress gene Q.
e. Cell B signaled to D only, causing it to express gene Q.
f. Cell 3 signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
g. Cell 3 signaled to C only, causing it to repress gene Q.
h. Cell 3 signaled to D only, causing it to express gene Q.

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Cell Fate: Knowledge Check (part 2)


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Introduction

From ve dierent individuals, you isolate cells A & B away


from cells 1-4. In each case you observe:

Objectives
Mechanisms
Scientific Method
Scenario
Summary

Back

What mechanism(s) might cause daughter cells C & D


to express dierent genes?
a. The dierence arose by chance.
b. Cell A was already asymmetric (because its mother was
asymmetric) and then divided asymmetrically.
c. Cell B signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
d. Cell B signaled to C only, causing it to repress gene Q.
e. Cell B signaled to D only, causing it to express gene Q.
f. Cell 3 signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
g. Cell 3 signaled to C only, causing it to repress gene Q.
h. Cell 3 signaled to D only, causing it to express gene Q.

Next

Cell Fate: Knowledge Check (part 3)


MENU
Introduction
Objectives
Mechanisms
Scientific Method

From ve dierent
individuals, you isolate
cells A & B away from
cells 1-4. And then, just
BEFORE cell A divides,
you isolate cell A away
from cell B. In each
case you observe:

Scenario
Summary

Back

What mechanism(s) might cause daughter cells C & D


to express dierent genes?
a. The dierence arose by chance.
b. Cell A was already asymmetric (because its mother was
asymmetric) and then divided asymmetrically.
c. Cell B signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
d. Cell B signaled to C only, causing it to repress gene Q.
e. Cell B signaled to D only, causing it to express gene Q.
f. Cell 3 signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
g. Cell 3 signaled to C only, causing it to repress gene Q.
h. Cell 3 signaled to D only, causing it to express gene Q.

Next

Cell Fate: Knowledge Check (part 4)


MENU
Introduction

From ve dierent individuals, you isolate the mother of cell A


- which you gure out is cell 0 - away from all other cells, just
BEFORE cell 0 divides. In each case you observe:

Objectives
Mechanisms
Scientific Method
Scenario
Summary

Back

What mechanism(s) might cause daughter cells C & D


to express dierent genes?
a. The dierence arose by chance.
b. Cell A was already asymmetric (because its mother was
asymmetric) and then divided asymmetrically.
c. Cell B signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
d. Cell B signaled to C only, causing it to repress gene Q.
e. Cell B signaled to D only, causing it to express gene Q.
f. Cell 3 signaled to A, causing A to localize an mRNA or protein
asymmetrically and then divide asymmetrically.
g. Cell 3 signaled to C only, causing it to repress gene Q.
h. Cell 3 signaled to D only, causing it to express gene Q.

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Cell Fate: Scientific Method


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scenario
Summary

The scientific method has several steps:


1. Observe a phenomenon.
2. Formulate a hypothesis to explain the
phenomenon.
3. Design one or more experiments to test
this hypothesis and distinguish it from
alternative possible explanations. What does
your hypothesis predict will be the result of
these experiments?
4. Perform these experiments - do the results
support or contradict your hypothesis? If
contradict, then formulate a new hypothesis
that is consistent with all your results and
return to step 3. If support, are these
experimental results also consistent with
alternative hypotheses? If so, return to step 3.
If not, you're done!

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Cell Fate: Activity Description


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

In this activity you will practice using the scientic


method to determine the mechanism by which two
sister cells (daughters of the same mother) end up
expressing dierent genes. You will:
Observe an example in which two sister cells
end up expressing different genes.
Formulate a hypothesis to explain this
phenomenon - make sure that it is consistent
with your observations in part 1!
Design experiments to test your hypothesis.

Interpret the results and decide whether your


hypothesis is supported or contradicted.

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Cell Fate: Scenario Hypotheses


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Introduction
Objectives

You isolate neighboring cells O and P from a


developing mouse kidney and watch what
happens:

Mechanisms
Knowledge Check
Scientific Method
Summary
You conclude (correctly!) that P must already
be asymmetric when you isolate it and that it
then divides asymmetrically, but you want to
understand why cell R expresses TF52 but its
sister cell S does not.

Now you need to


formulate a hypothesis
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Cell Fate: Scenario Hypotheses


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Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

Back

Choose a hypothesis:
1.
2.

This happens by chance.


Q is asymmetric because P is asymmetric. Q then divides
asymmetrically.
3. Q is asymmetric because its "bottom" half receives a signal from
W. Q then divides asymmetrically.
4. Q is symmetric, but only R receives a signal from W to activate
TF52 expression.
5. Q is symmetric, but only S receives a signal from W to repress
TF52 expression.
6. Q is symmetric, but only R receives a signal from O to activate
TF52 expression.
7. Q is symmetric, but only S receives a signal from O to repress
TF52 expression.
8. Q is symmetric, but only R receives a signal from X or Y to
activate TF52 expression.
9. Q is symmetric, but only S receives a signal from X or Y to
repress TF52 expression.

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Cell Fate: Scenario Experiments


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

You chose: This happens by chance.


Now select an experiment to perform. Click on the R button to view the
results of the experiment. After you see the results, ask yourself if they
support or contradict your hypothesis, then click on the I button to see
the interpretation.

R
Experiment III.
Isolate cell R
immediately before cell
W divides. Observe
which cell(s) express
TF52.
Experiment V. Isolate cells R
and S immediately after cell W
divides. Observe which cell(s)
express TF52.

Back

Experiment I. Repeat the original


experiment (in which you isolate O
& P and just observe which cell(s)
express TF52) ten more times.

R
I

R
I

Experiment II.
Isolate cell Q
immediately before
it divides. Observe
which cell(s) express
TF52.

Experiment IV.
Isolate cells R and S
immediately before
cell W divides.
Observe which cell
(s) express TF52.

R
I

Next

Cell Fate: Scenario Experiments


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

You chose: Q is asymmetric because P is asymmetric. Q then


divides asymmetrically.
Now select an experiment to perform. Click on the R button to view the
results of the experiment. After you see the results, ask yourself if they
support or contradict your hypothesis, then click on the I button to see
the interpretation.

R
Experiment III.
Isolate cell R
immediately before cell
W divides. Observe
which cell(s) express
TF52.
Experiment V. Isolate cells R
and S immediately after cell W
divides. Observe which cell(s)
express TF52.

Back

Experiment I. Repeat the original


experiment (in which you isolate O
& P and just observe which cell(s)
express TF52) ten more times.

R
I

R
I

Experiment II.
Isolate cell Q
immediately before
it divides. Observe
which cell(s) express
TF52.

Experiment IV.
Isolate cells R and S
immediately before
cell W divides.
Observe which cell
(s) express TF52.

R
I

Next

Cell Fate: Scenario Experiments


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

You chose: Q is asymmetric because its bottom half receives


a signal from W. Q then divides asymmetrically.
Now select an experiment to perform. Click on the R button to view the
results of the experiment. After you see the results, ask yourself if they
support or contradict your hypothesis, then click on the I button to see
the interpretation.

R
Experiment III.
Isolate cell R
immediately before cell
W divides. Observe
which cell(s) express
TF52.
Experiment V. Isolate cells R
and S immediately after cell W
divides. Observe which cell(s)
express TF52.

Back

Experiment I. Repeat the original


experiment (in which you isolate O
& P and just observe which cell(s)
express TF52) ten more times.

R
I

R
I

Experiment II.
Isolate cell Q
immediately before
it divides. Observe
which cell(s) express
TF52.

Experiment IV.
Isolate cells R and S
immediately before
cell W divides.
Observe which cell
(s) express TF52.

R
I

Next

Cell Fate: Scenario Experiments


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

You chose: Q is symmetric, but only S receives a signal from


W to repress TF52 expression.
Now select an experiment to perform. Click on the R button to view the
results of the experiment. After you see the results, ask yourself if they
support or contradict your hypothesis, then click on the I button to see
the interpretation.

R
Experiment III.
Isolate cell R
immediately before cell
W divides. Observe
which cell(s) express
TF52.
Experiment V. Isolate cells R
and S immediately after cell W
divides. Observe which cell(s)
express TF52.

Back

Experiment I. Repeat the original


experiment (in which you isolate O
& P and just observe which cell(s)
express TF52) ten more times.

R
I

R
I

Experiment II.
Isolate cell Q
immediately before
it divides. Observe
which cell(s) express
TF52.

Experiment IV.
Isolate cells R and S
immediately before
cell W divides.
Observe which cell
(s) express TF52.

R
I

Next

Cell Fate: Scenario Experiments


MENU
Introduction
Objectives
Mechanisms
Knowledge Check
Scientific Method
Summary

You chose: Q is symmetric, but only S receives a signal from


X or Y to represent TF52 expression.
Now select an experiment to perform. Click on the R button to view the
results of the experiment. After you see the results, ask yourself if they
support or contradict your hypothesis, then click on the I button to see
the interpretation.

R
Experiment III.
Isolate cell R
immediately before cell
W divides. Observe
which cell(s) express
TF52.
Experiment V. Isolate cells R
and S immediately after cell W
divides. Observe which cell(s)
express TF52.

Back

Experiment I. Repeat the original


experiment (in which you isolate O
& P and just observe which cell(s)
express TF52) ten more times.

R
I

R
I

Experiment II.
Isolate cell Q
immediately before
it divides. Observe
which cell(s) express
TF52.

Experiment IV.
Isolate cells R and S
immediately before
cell W divides.
Observe which cell
(s) express TF52.

R
I

Next

Cell Fate: Summary


MENU
Introduction
Objectives

Did you gure out which hypothesis was the


best, based on your observations and the
results of the experiments?

Mechanisms
Knowledge Check
Scientific Method

If you are ready for


the answer, click
here

Scenario
There are three mechanisms by which
daughter cells can express dierent genes:
by chance, asymmetric cell division, and
cell-cell signaling.

By using the scientic method, you can
gure out which mechanism is being used.

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