The dorsal gradient and the dorsoventral genetic regulatory hierarchy
(a) Different zygotic genes are expressed in different spatial domains along the D/V axis of the embryo. Some of these domains correspond to populations of cells that will give rise to distinct regions of the embryo (such as the mesoderm and neurogenic ectoderm). (b) The battery of genes regulated by Dorsal protein. (c) Dorsal regulation of target genes is dependent on threshold concentrations of protein. The concentration of nuclear Dorsal protein is highest in ventral (V) cells and lowest in dorsal (D) cells. Certain target genes are activated at different concentrations of Dorsal (thresholds 1, 2, and 3).
Source: Adapted from Gilbert S. Developmental biology, 5th edn. Sunderland: Sinauer Associates. 1997; Jiang J, Levine M. Cell 1993; 72: 741-752.
The sharpness of the expression boundaries of the zygotic D/V patterning genes is refined by further regulatory interactions. The snail(sna) gene enhancer, which is bound by Dl, also requires the product of the twist (twi) gene to be activated. Synergistic interactions between Dl and Twi ensure a sharp on/off border of sna expression, which coincides with the boundary between and regulates the differentiation of the mesoderm from the neuroectoderm (Fig. 3.9c). The rhomboid(rho) element is repressed by the Snail protein, which eliminates rho expression from the mesoderm and restricts it to the neuroectoderm (Fig. 3.9c). A cascade of subsequent interactions, involving primarily the activity of the Dpp signaling molecule, further subdivides the dorsal region of the embryo.
In Drosophila and many other animals, the spatial and temporal expression patterns of individual Hox genes are much more complicated than those of most segmentation or D/V axis-patterning genes. The number of czs-elements and trans-acting regulators for each gene is therefore considerably greater for the Hox genes. The regulation of Hox gene expression has the following major features:
• Activation in a broad domain, usually consisting of two or more parasegments
• Modulation of the levels of expression within this domain
• Expression in all three germ layers, often in patterns that are slightly out of register between each germ layer
• Dynamic changes in the level and domains of expression throughout the subsequent course of development
Numerous transcription factors act on Drosophila Hox genes; likewise, many cz's-acting regulatory elements control the various features of Hox expression. In the embryonic ectoderm, for example, most Hox genes are regulated by as many as six classes of regulators. All three classes of zygotic segmentation genes are involved in Hox regulation. Gap proteins regulate the broad initial domains of Hox transcription, selected pair-rule proteins are involved in setting the initial spatial register of certain Hox gene domains, and segment polarity proteins, such as the Engrailed protein, help provide intrasegmental modulation of Hox gene expression levels. A fourth level of control involves other Hox proteins—the posterior boundaries and levels of expression of some Hox genes are regulated by more posteriorly acting Hox proteins. A fifth level of control involves autoregulatory feedback mechanisms that operate to maintain Hox expression domains. Finally, a large group of chromatin-associated proteins, termed the Polycomb group and Trithorax group of proteins, act to maintain the repressed or activated transcriptional state, respectively, of many Hox genes (Fig. 3.10).
The Ultrabithorax gene provides a good example of the constellation of cz's-regulatory elements that control Hox gene expression. Different czs-elements of Ubx control expression in particular parasegmental domains, in a manner analogous to individual pair-rule stripe elements (Fig. 3.11). These elements contain binding sites for several activators and repressors. The pattern of Ubx expression controlled by these elements is the net output from numerous positive and negative inputs. Other Ubx elements control the level of expression within parts of parasegments, in appendage fields later in development, and in other germ layers such as the mesoderm (Fig. 3.11).
Segment polarity proteins
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