The segmental subdivision of the head is one of the more dramatic examples of how genes work to define specific strucures. Each segment of the head is determined by a set of genes whose transcription is directed to that segment.

ocelliless, often called orthodenticle (otd) is essential for defining the antennal segment, which determines both the eye and the antenna, as well as parts of the brain. empty spiracles, buttonhead and sloppy paired are also required to define the antennal segment. otd can be considered a gap gene since it is activated by bicoid and torso in a very narrow band in the developing head, and mutation of otd specifically eliminate certain adult head structures. In the eye antennal disc, otd is expressed in a very specific manner to define areas of the dorsal head [Images], including ocelli, eye and bristles. otd expression areas that define ocelli and bristles are neither in the eye or antennal anlagen of the eye-antennal disc, but rather in a third area, a circumferential segment of the eye disc (Royet, 1995).

hedgehog and wingless have an role in specifying adult head structures. Reduction of hedgehog activity results in flies completely lacking medial head structures, while loss of wingless results in deletion of lateral (orbital) and mediolateral (frons) head structures. Ectopic expression of hh results in the induction of ectopic ocelli at more lateral locations, while ectopic wg results in an invasion of mediolateral frons cuticle into the ocellar region. In otd mutants, specifically ocelliless regulatory mutations, wg expression fails to disappear from the medial region and instead persists across the entire primordium of the head vertex. At the same time, hh expression in lost. In a complementary fashion, hh also seems to have a positive effect on otd expression; ectopic hh activates otd suggesting that otd expression in the head vertex primordium may be activated by hh during normal eye-imaginal disc development. Thus otd is required for regional head development, and has a critical role in regulating wg and hh expression (Royet, 1996).

The effect of otd on bristle structures is the basis for its name, which might be loosely translated as "correctly toothed (bristled)." Otd's effects on neural tissues are not confined to the head, since it is also involved in specifying particular neurons in the ventral midline of the central nervous system.

The mechanisms ofaction of cephalic gap genes remain poorly understood. orthodenticle (otd), whichestablishes a specific region of the anterior head, has been proposed to act in a combinatorial fashion with thecephalic gap genes empty spiracles (ems) and buttonhead (btd) to assign segmental identities in this region. To test thismodel, a heat-inducible transgene was used to generate pulses of ubiquitous otd expression during embryonicdevelopment. Ectopic otd expression causes significant defects in head formation, including the duplication of sensorystructures derived from otd-dependent segments. However, these defects do not appear to result from thetransformation of head segment identities predicted by the combinatorial model. To determine if the combinatorial model is correct, focus was placed on the dorsomedial papilla (dmp), antennal sense organ (anso), and dorsolateral papilla (dlp). The epidermal portions of these structures serve as markers of the ocular, antennal, and intercalary segments, respectively. According to the combinatorial model, ubiquitous otd expression should cause a transformation of the intercalary segment to a second antennal segment, without affecting the identity of the more anterior ocular segment. This would be indicated by duplication of the anso, loss of the dlp, and no change in the dmp. In a significant fraction of the cuticles that developed after an early pulse of otd expression, the anso is indeed duplicated. Significantly, however, the dlp is generallly not lost in these embryos, indicating that at least part of the intercalary segment is still present. These results do not indicate a transformtion of segmental identity, but rather the specific duplication of otd-dependent sensory structures (Gallitano-Mendel, 1998).

It is likely that misexpression of otd causes intrasegmental transformations rather than intersegmental transformations. The results correlate with specificregulatory effects of otd on the expression of the segment polarity genes engrailed (en) and wingless (wg). In wild-type embryos, en is expressed in each of the head segments. In the anterior head, en expression first appears during germ band extension in the antennal primordium, as a stripe 1-2 cells in width. Expression subsequently appears in the ocular segment (a small spot), the intercalary segment (a small stripe), and eventually in the clypeolabral region. Early induction of otd causes a broadening of the en antennal stripe to a width of as many as eight cells. In wild-type embryos, wg expression first apppears in the forgut primordium at the blastoderm stage. Subsequently, a broad anterior cephalic stripe forms. Following germ-band extension, wg is activated in a discrete stripe or spot in each head segment, anterior and adjacent to the engrailed counterpart. Ubiquitous otd expression causes the reduction or loss of wg in the antennal, intercalary, gnathal, and trunk segments. More anterior wg expression in the forgut, clypeolabral region, and ocular segment is not reduced (Gallitano-Mendel, 1998).

Mutant embryonic cuticles were examined for en or wg: en mutant embryos lack ansos; wg mutant embryos exhibit severe disruptions in head formation. However, unlike in en embryos, the anso is not missing but instead is frequently duplicated. These results indicate that en is required for anso formation. They also suggest that wg plays an inhibitory role in the specification of this sensory strucure. In double en;wg mutant embryos, the anso is absent, indicating that, although the absence of wg permits the formation of multiple ansos, this requires en activity. Although ubiquitous otd represses wg expression in the antennal segment and all segments posterior to it, otd induction has the opposite effect in the ocular segment, positively regulating wg expression. It is concluded that cephalic gap genes define head morphology through the direct modulation of segment polarity gene expression (Gallitano-Mendel, 1998).

Ectopic otdexpression also causes the loss of head structures derived from the maxillary segment, which lies posterior to the otddomain. Ubiquitous otd affects the cirri and maxillary sense organ. This effect is associated with otd repression of the homeotic selector gene Deformed (Dfd). While Dfd mutants lack mouth hooks, the maxillary sense organ, cirri, and the ventral organ, it has been shown that otd induction reduces the number of cirri and maxillary sense organ papillae, but does not eliminate them altogether (Gallitano-Mendel, 1998).

Bases in 5' UTR - 777

Exons - 4

Bases in 3' UTR - 1018

Structural Domains

The homeodomain is paired-group-like, but OTD lacks a paired domain (Finkelstein, 1990).