The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of genes coding specific transcription factors. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the embryo. Their protein products which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves.
Once established, these overlapping gap protein gradients provide
spatial cues which generate the repeated
pattern of the subordinate pair-rule gene expression. The maternal
gene products, in combination with various gap gene proteins, provide
position-dependent sets of transcriptional activator/repressor systems
which regulate the spatial pattern of specific expression of downstream
genes, such as pair-rule and segment polarity genes. Region-specific
combinations of different transcription factors that derive from localized
gap gene expression eventually generate the periodic pattern of
pair-rule gene expression by the direct interaction with individual regulatory
"stripe elements" of particular pair-rule gene promoters. Thus,
the developmental fate of early embryo cells is programmed according to
their position within the anterior-posterior axis of the embryo: maternal
transcription factors regulate the region-specific expression of first
zygotic transcription factors, which, by their specific and unique combinations,
control subordinate zygotic transcription factors, thereby subdividing
the embryo into increasingly smaller units later seen in the larva. Investigated
in details, core part of the segmentation net containing gap genes
is shown in Fig.1.
Fig.1. As represented in the picture, (bicoid) bcd activates both (hunchback) hb and (Kruppel)Kr, hb activates and represses Kr in a concentration-dependent manner and represses the anterior limits of both (knirps) kni and (giant) gt expression, while the terminal gap genes (tailless) tll and (huckebein) hkb act as repressors of Kr, kni abd gt. Tll is also required to activate posterior hb gene expression. Kni and possibly gt is thought to be activated by global activator system for which no genetic basis is established (Jackle et al., 1992). Hkb and tll in turn are activated by the terminal signal transduction pathway.
Fig.2. Schematic presentation of the gap gene cascade expression along the longitudinal axis of early fruit fly embryo.
It is well established that each segmentation gene has vast regulatory sequences containing multiple target sites for regulation of their activity. Multiple interactions of negatively acting transcription factors are directly responsible for setting the spatial limits of expression. But what is more, they probably do so by interfering with the cooperative binding of positively acting factors which react at nearby target sites. For example, the anterior limit of knirps gene expression is set by five or six interactions with regulatory sites to which the negatively acting HUNCHBACK (HB) protein binds, and the posterior limit requires multiple negative interactions at a different regulatory locus with the product of the gap gene tll (Pankratz et al., 1992). Similarly there are seven sites of HB interaction in the PBX control region of the Ubx gene. These negative interactions are required to set the spatial limits of a band of Ubx expression (Zhang et al., 1991; Qian et al., 1991), and they apparently function antagonistically with a generally distributed positive transcription factor that binds to nearby target sites.
FIG.3.
By deletion analysis of the Kr cis-acting sequences, one defined a 730-bp minimal Kr DNA sequence which is sufficient to mediate gene expression in the authentic early Kr expression domain (Hoch et al., 1990; 1991). The corresponding DNA fragment, termed Kr730-element, contains the cis-acting requirement for the activation of gene expression in response to BCD, and the target sites for the interactions with the gap gene proteins HB, KNI, GT and TLL.
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