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

MECHANISMS OF PATTERN FORMATION
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(A)
(C)
wild type
Hox gain of function
family of transcription regulators that we encountered in Chapter 7. These proteins
drive cells to differentiate into muscle, expressing muscle-specific actins
and myosins and all the other specialized cytoskeletal, metabolic, and membrane
proteins that a muscle cell needs. Analogously, members of the Achaete/Scute
family of transcription regulators drive cells to become neural progenitors. In
both these examples, the proteins belong to the basic helix–loop–helix (bHLH)
class of transcription regulators (see p. 377), and the same is true for many of the
other proteins that induce the differentiation of particular cell types. These master
transcription regulators exert their powerful differentiation-inducing activity by
binding to many different regulatory sites in the genome and thereby controlling
the expression of large numbers of downstream target genes. In one well-studied
case, that of an Achaete/Scute family member called Atonal homolog 1 (Atoh1),
the number of direct target genes in the mouse genome is more than 600. It is
important to note, however, MBoC6 that even m22.48/22.33 such powerful drivers of cell differentiation
can have radically different effects according to the context and history of the cells
in which they act: Atoh1, for example, drives differentiation of certain classes of
neurons in the brain, of sensory hair cells in the inner ear, and of secretory cells in
the lining of the gut.
Other genes encoding transcription regulators can drive the formation and
assembly of the multiple cell types that constitute an entire organ. A famous
example is the transcription regulator Eyeless. When it is artificially expressed in a
patch of cells in the leg precursors of Drosophila, a well-organized eye-like organ
develops on the leg, with the various eye cell types correctly arranged (see Figure
7–35B); conversely, loss of the Eyeless gene results in flies that lack eyes. Moreover,
loss of the Eyeless homolog Pax6 in vertebrates likewise leads to loss of eye
structures. Similar organ-selector proteins are known for foregut, heart, pancreas,
and other organs. They are all master transcription regulators that directly regulate
hundreds of target genes, the products of which then specify and construct
the different elements of the appropriate organ. However, as in the example of
Atoh1, they usually exert their specific effect only in combination with the right
partners, which are only expressed in cells that were appropriately primed during
their earlier development.
(B)
(D)
13th rib
lumbar
wild type
13th rib
sacral
Hox loss of function
Figure 21–33 Control of anteroposterior
pattern by Hox genes in the mouse.
(A,B) A normal mouse (wild type) has
about 65 vertebrae, differing in structure
according to their position along the
body axis: 7 cervical (neck), 13 thoracic
(with ribs), 6 lumbar [bracketed by yellow
asterisks in (B)], 4 sacral [bracketed by red
asterisks in (B)], and about 35 caudal (tail).
(A) shows a side view and (B) shows a
dorsal view; for clarity, the limbs have been
removed in each picture.
(C) The HoxA10 gene is normally
expressed in the lumbar region (together
with its paralogs HoxC10 and HoxD10);
here it has been artificially expressed in
the developing vertebral tissue all along
the body axis. As a result, the cervical and
thoracic vertebrae are all converted to a
lumbar character. (D) Conversely, when
HoxA10 is removed along with HoxC10
and HoxD10, vertebrae that should
normally have a lumbar or sacral character
take on a thoracic character instead. (A and
C, from M. Carapuço et al., Genes Dev.
19:2116–2121, 2005. With permission
from Cold Spring Harbor Laboratory
Press; B and D, from D.M. Wellik and
M.R. Capecchi, Science 301:363–367,
2003.)
Notch-Mediated Lateral Inhibition Refines Cellular Spacing
Patterns
After the establishment of the basic body plan and the generation of organ precursors,
many further steps of pattern refinement are required to achieve the adult
pattern of terminally differentiated cells in tissues and organs. As we discussed