Drosophila has been the foremost model organism for the study of the genetics of animal development. Its embryonic pattern is initiated by the products of maternal-effect genes called egg-polarity genes, which operate by setting up graded distributions of transcription regulators in the egg and early embryo. The gradient of Bicoid protein along the A-P axis, for example, helps initiate the orderly expression of gap genes, pair-rule genes, and segment-polarity genes. These three classes of segmentation genes, through a hierarchy of interactions, become expressed in some regions of the embryo and not others, progressively subdividing the embryo along the A-P axis into a regular series of repeating modular units called segments.
Superimposed on the pattern of gene expression that repeats itself in every segment, there is a serial pattern of expression of Hox genes that confer on each segment a different identity. These genes are grouped in complexes and are arranged in a sequence that matches their sequence of expression along the A-P axis of the body.
Although Hox gene expression is initiated in the embryo, it is subsequently maintained by the action of chromatin-binding proteins of the Polycomb and Trithorax group, which stamp the chromatin of the Hox complex with a heritable record of its embryonic state of repression or activation, respectively. Hox complexes homologous to that of Drosophila are found in virtually every type of animal, where they help pattern the A-P axis of the body.
Signaling gradients are also set up along the dorsoventral (D-V) axis. Initially, Toll signaling generates a nuclear gradient of Dorsal protein, which induces an extracellular signaling gradient of the TGFβ-family protein Dpp and its antagonist,
Figure 21–37 Morphological diversity in stickleback fish is caused by changes in regulatory elements.
(a–D) pelvic spines are present in marine (a) but not in freshwater (c) populations. correspondingly, Pitx1 is expressed in the pelvic area in marine (B) but not in freshwater (D) fish. the lack of expression in the pelvic area of freshwater populations is caused by mutations in an enhancer element. Other enhancers and sites of expression for Pitx1 are the same in marine and freshwater sticklebacks. (courtesy of Michael D. Shapiro.)
Sog. This creates a gradient of Dpp activity that helps refine the assignment of different characters to cells at different positions along the D-V axis.
In Xenopus, the polarity of the egg and the site of sperm entry set up the embryonic axes. A gradient generated by the TGFβ-family protein Nodal induces different fates along the animal-vegetal axis, whereas BMP and Chordin—proteins homologous to Drosophila Dpp and Sog, respectively—control the patterning of the D-V axis. This axis is inverted, so that dorsal in the fly corresponds to ventral in the frog.
Transcription regulators control the formation of specific cell types. Members of the MyoD/myogenin family drive the process of muscle cell determination, coordinating the many components required, whereas Achaete/Scute transcription regulators control neural fate. Other genes encoding such master transcriptional regulators can regulate the formation of entire organs. Eyeless, for example, is both necessary and sufficient to generate eye structures in Drosophila.
To refine the anatomical pattern within such an organ, the cells interact locally, both by diffusible inductive signals and by short-range mechanisms. Often, the cells compete with one another by lateral inhibition. This process results in activation of the Notch signaling pathway in one cell and inhibition in its neighbors, generating two different cell types. Asymmetric cell divisions, in which daughter cells inherit different molecular determinants from the mother cell, provide an additional way to organize a fine-grained diversity of cell types.
Evidence from recent evolutionary events indicates that anatomical changes are mostly driven by changes in regulatory DNA sequences that determine when and where developmental genes are expressed. How the striking diversity in body structures has evolved over longer times remains largely unknown, although it seems likely that similar principles apply.