The Interactive Fly
Zygotically transcribed genes
Hedgehog Signaling Pathway Database
Pattern formation takes place through a series of logical steps, reiterated many times over during the development of an organism. Viewed from a broader evolutionary perspective, across species, the same sorts of reiterative pattern formations are seen. The central dogma of pattern formation has been described by Lawrence and Struhl (1996) in an article entitled "Morphogens, Compartments and Pattern: Lessons from Drosophila." Three interlocking and overlapping steps are defined: first, positional information in the form of morphogen gradients allocate cells into nonoverlapping sets, each set founding a compartment. Second, each of these compartments acquires a genetic address, as a result of the function of active "selector" genes that specify cell fate within a compartment and also instruct cells and their descendents how to communicate with cells in neighboring compartments. The third step involves interactions between cells in adjacent compartments, initiating new morphogen gradients, which directly organize the pattern.
Taking these steps in greater detail, one finds the first step in patterning to be the definition of sets of cells in each primordium. Cells are allocated according to their positions with respect to both dorsoventral and anterior/posterior axes by morphogen gradients. Allocation of cells in the dorsoventral axis constitutes the germ layers, such as mesoderm or neurectoderm. This function is carried out by the gene dorsal and its targets. Subdivision of the anterior/posterior axis into segmental units known as parasegments is carried out by gap and pair rule genes.
In segmentation, the second step (the specification of cell fate in each compartment) is carried out by the gene engrailed and elements of the bithorax complex. engrailed defines anterior and posterior compartments both in segmentation and in limb specification.
The wing disc provides an excellent example of pattern formation in Drosophila. During the larval period, both anterior and posterior compartments are subdivided by the apterous selector gene, which is activated in dorsal and repressed in ventral cells. Selector genes do much more than specify the pattern and structures that the compartments will eventually make - they also specify, indirectly, a surface property termed cell affinity. Cells that share the same affinity can intermingle during growth, while cells in the neighboring compartment, with a different basis for affinity, also self-associate but minimize contact with cells in adjacent compartments; in this way, a well defined boundary forms between adjacent compartments. In wing compartment definition, alternative integrins function in different compartments determining mutual and exclusive affinity.
The third step in pattern formation, secretion of morphogens, functions to differentiate patterns within compartments (and thereby establish segment polarity). Initially all cells within a compartment are equipotent, but they become diversified to form pattern. Pattern formation depends on gradients of morphogens, gradients initiated along compartment boundaries. How are these gradients established? A short-range signal is induced in all the cells of the compartment in which a selector gene (engrailed) is active. For segment polarity this signal is Hedgehog. In the adjacent compartment the selector gene is inactive, ensuring that the cells are sensitive to the signal. The Hedgehog signal range is probably only a few rows of cells wide; responding cells become a linear source of a long-range morphogen that diffuses outward in all directions.
The long range signal in wing segment polarity is Decapentaplegic. Two targets of DPP are spalt and optomotor blind, both transcription factors activated by DPP. A graded distribution of DPP outside of cells organizes a graded distribution of the domains of spalt and omb, which in turn generate the patterning of elements such as bristles, arranged according to transcription factor concentration.
In the wing disc apterous functions as a selector gene that makes the dorsal surface distinct from the ventral surface. Apterous has at least two functions: first it is responsible for making the dorsal cell type distinct from the ventral, a property that may be due to its activation of gene Dorsal wing; second, it directs the expression of fringe and Serrate in the dorsal compartment and by its absence, Notch in the ventral compartment. It could be that wingless is the long-range morphogen induced by Serrate action on Notch. Fringe functions as a short range secreted signal. In embryonic segmentation, the long range signal is unknown, but may again be wingless.
Lawrence, P. A. and Struhl, G. (1996). Morphogens, compartments and pattern: Lessons from Drosophila. Cell 85: 951-961
Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.
The Interactive Fly resides on the
Society for Developmental Biology's Web server.