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neuron. These genes are organized in a complex of four
( achaete; scute; asense; and lethal of scute ) at a single locus
in Drosophila (Alonso and Cabrera, 1988). Deletion of
this locus results in the absence of most of the neuro-
blasts in the fly, in both the central and peripheral
nervous systems (Cabrera et al., 1987), while animals
with extra copies of these genes have ectopic neurons
and sense organs (Brand and Campos-Ortega, 1988).
Since these genes are required for the formation of
neurons from the epidermal cells, they have been called
the “proneural genes” (Figure 1.26) An additional
achaete scute -related gene, atonal , is a proneural gene for
the internal chordotonal sensory organs and the eye
(Jarman et al., 1993).
How do the proneural genes function in neuroblast
segregation? The proneural genes code for transcrip-
tion factors of a particular class, known as the b asic-
h elix- l oop- h elix, or bHLH , family. These proteins bind
to specific short stretches of DNA, known as E-boxes,
in the promoters of target genes, and activate their
transcription. Proneural bHLH transcription factors are
members of a broader class of tissue-specific tran-
scription factors (class B). Other tissues, like muscle,
also have class B transcription factors, but instead of
activating neural genes, the muscle-specific bHLH pro-
teins activate muscle-specific genes. The first of these
that was discovered was called MyoD , for myogenic
determination factor. These tissue-specific class B
transcription factors bind DNA as dimers; their dimer
partners are similar, but more ubiquitously expressed,
bHLH genes, known as class A. In Drosophila the class
A gene is called daughterless (Da), named for its role in
the sex determination process (Caudy et al., 1988). The
dimerization occurs through one of the helices (Figure
1.27), while the basic region is an extension of the other
helix and interacts with the major groove of the DNA.
The achaete scute transcription factors are thought to
bind to E-boxes in the promoter regions of neuroblast-
specific genes and activate their transcription, main-
taining that cell as a neuroblast.
The process of neuroblast formation requires that a
precise number of cells from the neurogenic region
delaminate. Just prior to the delamination of the neu-
roblasts, achaete is expressed in a group of four to six
epidermal cells (Skeath and Carrol, 1992; Figure 1.25).
A combination of upstream regulatory genes act on the
promoter regions of the achaete scute genes to induce
their expression in these regularly spaced clusters of
cells along the neurogenic region (Skeath et al., 1992).
The four to six cells that express achaete scute are
known as the proneural cluster, and they all have
Wild type
Neuroblasts
Helix 1
Proneural mutant
Neurogenic mutant
Loop
Neuroblasts
Helix 2
DNA
FIGURE 1.26 Neurogenic genes and proneural genes were first
identified in the Drosophila due to their effects on neural develop-
ment. In the wild-type embryo (top), only one neuroblast (red)
delaminates from a given proneural cluster in the ectoderm.
However, in flies mutant for proneural genes (middle), like achaete
scute , no neuroblasts form. By contrast, in flies mutant for neuro-
genic genes (bottom), like Notch and Delta , many neuroblasts delam-
inate at the positions where only a single neuroblast develops in the
wild-type animal. Thus, too many neurons delaminate—hence the
name “neurogenic.”
Basic domain
FIGURE 1.27 Several critical proteins that are necessary for the
development of specific cell and tissue types are members of the
bHLH transcription factor family of molecules. bHLH denotes the
b asic- h elix- l oop- h elix” structure of these molecules. The bHLH
transcription factors dimerize via their first helix and interact with
DNA via their second helix and their basic region.
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