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Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

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MOLECULAR GENETIC MECHANISMS THAT CREATE AND MAINTAIN SPECIALIZED CELL TYPES

397

LEFT

embryonic cell

INDUCTION OF REGULATOR TRANSCRIPTION

cell division

cell A

INDUCTION OF REGULATOR TRANSCRIPTION 2

1

1

cell B

AND 3

RIGHT

Figure 7–33 The importance of

combinatorial gene control for

development. Combinations of a few

transcription regulators can generate many

cell types during development. In this

simple, idealized scheme, a “decision” to

make one of a pair of different transcription

regulators (shown as numbered circles)

is made after each cell division. Sensing

its relative position in the embryo, the

daughter cell toward the left side of the

embryo is always induced to synthesize the

even-numbered protein of each pair, while

the daughter cell toward the right side of

the embryo is induced to synthesize the

odd-numbered protein. The production of

each transcription regulator is assumed to

be self-perpetuating once it has become

initiated (see Figure 7–39). In this way,

through cell memory, the final combinatorial

specification is built up step by step. In this

purely hypothetical example, five different

transcription regulators have created eight

final cell types (G–N).

2

3

1 2

1

3

cell C cell D cell E cell F

INDUCTION OF REGULATOR TRANSCRIPTION

4

AND

5

2 4

2

5

3

4

3

5

1

4

2 1 2

5

1

4

3

1

5

3

cell G cell H cell I cell J cell K cell L cell M cell N

combinatorial control of the muscle-specific genes, and the addition of MyoD

completes the unique combination required to direct the cells to become muscle.

An even more striking example is seen by artificially expressing, early in development,

a single Drosophila transcription regulator (Eyeless) in groups of cells

MBoC6 m7.76/7.34

(A)

(B)

50 µm 50 µm

Figure 7–34 A small set of transcription regulators can convert one differentiated cell type

into another. In this experiment, (A) liver cells grown in culture were converted into (B) neuronal

cells via the artificial expression of three nerve-specific transcription regulators. Both types of cells

express an artificial red fluorescent protein, which is used to visualize them. This conversion involves

the activation of many nerve-specific genes as well as the repression of many liver-specific genes.

MBoC6 e8.16/7.35

(From S. Marro et al., Cell Stem Cell 9:374–382, 2011. With permission from Elsevier.)

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