BIOLOGICAL OVERVIEW

Bifid, more familiarly known as Optomotor blind, and T-related gene (Brachyenteron) are two Brachyury homologs in the fly. Brachyury has a major role in vertebrates in the differentiation of the notochord and in the formation of the mesoderm. optomotor blind is involved in differentiation of the brain, the CNS, the wing and in patterning of adult abdominal segments. These are all epidermally derived tissues. In the nervous system, omb is found in both neurons and glia.

Optomotor blind plays a prominent role in control of cell fate and polarity in the adult segments of Drosophila. Each abdominal segment produces a large dorsal cuticular plate (the tergite) and a smaller ventral plate (the sternite). Each tergite can be divided into three regions: an acrotergite that contains undecorated sclerotized cuticle, a central region containing an array of microchaetes, and a posterior region that contains a dark pigment band as well as a row of large macrochaetes at the posterior edge of this posterior region. All of the tergite, except the acrotergite, is covered with trichomes. For convenience, the posterior boundary of the tergite is defined to be the posterior edge of the pigment band. The intertergal cuticle is unpigmented and composed of an anterior trichome-bearing region (the posterior hairy zone or PHZ) and a posterior region of naked cuticle (the intersegmental membrane or ISM). All trichomes and bristles in the abdomen are oriented from the anterior to the posterior. The tergite and anterior portion of the PHZ develop from the anterior dorsal histoblast nest; the rest of the PHZ and the ISM develop from the posterior dorsal nest (Kopp , 1997).

Hedgehog protein secreted by posterior compartment cells plays a key role in patterning the posterior portion of the anterior compartment in adult abdominal segments. This patterning function of Hh is mediated by optomotor-blind. omb- mutants mimic the effects of loss-of-function alleles of hh: structures from the posterior of the anterior compartment are lost; often this region develops as a mirror image of the anterior portion. Structures from the anterior part of the posterior compartment are also lost. In the pupa, omb expression in abdominal histoblasts is highest at or near the compartment boundary, and decreases in a shallow gradient toward the anterior. This gradient is due to activation of omb by Hh, secreted by posterior compartment cells. In contrast to imaginal discs, this Hh signaling is not mediated by dpp or wg. Several hh gain-of-function alleles have been described that cause ectopic expression of omb in the anterior of the segment. Most of these cause the anterior region to develop with posterior characteristics without affecting polarity. However, an allele that drives high level ubiquitous expression of omb (QadroondFab) causes the anterior tergite to develop as a mirror-image duplication of the posterior tergite, a pattern just the opposite of that seen in omb- mutants. The Qd Fab allele has a dramatic effect on both polarity and bristle patterning. In Qd Fab hemizygotes and heterozygotes, the anterior tergite and intersegmental membrane (ISM) are deleted and replaced with a mirror-image duplication of the posterior tergite and PHZ. Ectopic macrochaetes are often, but not always, present at the anterior edge of the duplicated tergite structures, and sometimes also in the central tergite. The lines of polarity reversal are not fixed precisely with respect to cuticular pattern. In the most extreme phenotype, polarity is reversed exactly in the middle of the tergite and in the middle of the PHZ. More frequently, the line of polarity reversal is shifted anteriorly in the tergite and posteriorly in the PHZ. The phenotype is stronger in hemizygous males than heterozygous females, and is stronger in more posterior segments. The intertergal region is often compressed, and the dorsal longitudinal muscles underlying the tergites show irregular spacing and attachment sites (Koop, 1997).

omb alleles cause defects that are reciprocal to those of the Qd alleles. Hemizygotes for omb loss-of-function alleles mostly die as late larvae or early pupae; only a small percentage survive to the late pharate adult stage. Among the latter, the loss of structures that lie within the posterior region of the anterior compartment and the anterior region of the posterior compartment have been observed. In many hemisegments, especially those more anterior in the animal, posterior tergite and PHZ are deleted and replaced with a mirror-image duplication of the anterior tergite. This phenotype is exactly reciprocal to the phenotype of Qd Fab (Koop, 1997).

Ubiquitous expression of hh causes double-posterior patterning similar to that of Qd gain of function alleles. omb- alleles suppress this effect of ectopic hh expression and posterior patterning becomes independent of hh in the QdFab mutant. These observations indicate that omb is the primary target of hh signaling in the adult abdomen. However, it is clear that other targets exist. One of these is likely to be Scruffy, a novel gene, which acts in parallel to omb. To explain the effects of omb alleles, it is proposed that both anterior and posterior compartments in the abdomen are polarized by underlying symmetric gradients of unknown origin. It is suggested that omb has two functions: (1) it specifies the development of appropriate structures both anterior and posterior to the compartment boundary and (2) it causes cells to reverse their interpretation of polarity specified by the underlying symmetric gradients (Koop, 1997).

GENE STRUCTURE

optomotor blind DNA spans about 120 kb; the transcript extends 80 kb, with a 40 kb 3' regulatory region (Pflugfelder, 1990, 1992a and 1993).

PROTEIN STRUCTURE

Amino Acids - 974

Optomoter blind is a T-box DNA-binding protein. The T-box family is an ancient group that appears to play a critical role in development in all animal species. These genes were uncovered on the basis of similarity to the DNA binding domain of murine Brachyury (T) gene product, the defining feature of the family. Common features shared by T-box family members are DNA-binding and transcriptional regulatory activity, a role in development and conserved expression patterns, most of the known genes in all species being expressed in mesoderm or mesoderm precursors.

date revised: 3 DEC 97 

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