Disease relevance of oc

• Podocoryne polyps have no striated muscle and no Otx expression; both appear only during the asexual medusa budding process [1].
• To investigate the molecular basis of brain evolution, we searched for otd/Otx-related homeobox genes in the planarian Dugesia japonica, and identified two genes, DjotxA and B, whose expression appears to be restricted to the cephalic ganglion (brain) [2].

High impact information on oc

• Drosophila bearing the ocelliless mutation underproduce two major chorion proteins both of which map near this gene [3].
• The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors [4].
• Three Drosophila genes have been identified that are important in controlling the development of the head, two of which, empty spiracles and orthodenticle, have been cloned and shown to contain a homeobox [5].
• The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila head development [6].
• We also show that otd expression responds to the activity of the maternal tor gene at the anterior pole of the embryo [6].

Biological context of oc

• Ectopic orthodenticle expression alters segment polarity gene expression but not head segment identity in the Drosophila embryo [7].
• To test this model, we used a heat-inducible transgene to generate pulses of ubiquitous otd expression during embryonic development [7].
• Here we investigate the relevance of runt's activity as a repressor of otd in normal Drosophila embryogenesis otd expression is activated in the posterior region of embryos that are mutant for runt [8].
• Ectopic expression of the pair-rule gene runt in the anterior end of the Drosophila embryo antagonizes transcriptional activation of the head gap gene orthodenticle (otd) by the anterior morphogen bicoid [8].
• We report here that the homeobox gene orthodenticle (otd), which is involved in head development, could be such a gene [6].

Anatomical context of oc

• The homeoprotein Orthodenticle acts through these sites to activate rh3 and rh5 in their specific ommatidial subclass and through the same sites to prevent rh6 expression in outer photoreceptors [9].
• We show here that otd is necessary for the formation of the embryonic central nervous system (CNS). otd mutations result in the formation of an abnormal neuropil and in the disappearance of identified neurons associated with the midline of the CNS [10].
• We have identified a transcription unit corresponding to the otd locus and find that it is expressed early in a stripe near the anterior pole of the cellular blastoderm and later in the region of the CNS from which these neurons normally arise [10].
• Studies on expression and function of key developmental control genes suggest that the embryonic vertebrate brain has a tripartite ground plan that consists of a forebrain/midbrain, a hindbrain and an intervening midbrain/hindbrain boundary region, which are characterized by the specific expression of the Otx, Hox and Pax2/5/8 genes, respectively [11].
• Otx1 and Otx2, the murine homologs of the Drosophila orthodenticle gene, play a remarkable role in specification and regionalization of forebrain and midbrain [12].

Associations of oc with chemical compounds

• Pem, paired class member orthodenticle, and the bicoid maternal gene product homeodomains all have lysine residues at a recognition helix position implicated in DNA-binding specificity [13].
• These proteins can potentiate transactivation by P-Lim/Lhx-3 and are required for a synergistic activation of the glycoprotein hormone alpha-subunit promoter by P-Lim/Lhx3 and a pituitary Otx class homeodomain transcription factor, with which they also specifically associate [14].
• A recently identified gene, hclA (synonym: ort), codes for an ionotrophic histamine receptor subunit in Drosophila melanogaster, and known hclA mutations lead to defects in the visual system, neurologic disorders and changed responsiveness to neurotoxins [15].

Regulatory relationships of oc

• Epidermal growth factor receptor signaling activates orthodenticle expression during Drosophila head development [16].
• We also demonstrate that otd is activated by wg in the vertex primordium [17].
• Finally, we identify a novel pathway mediated by the gap gene huckebein through which three maternal systems cooperate to repress otd expression at the anterior terminus of the embryo [18].
• In the eye-antennal imaginal disc, dve is coexpressed with oc in the region that gives rise to the head capsule and is active along the medial edge of the antennal disc and in the first antennal segment [19].

Other interactions of oc

• Loss of tll function results in the absence of all protocerebral neuroblasts, otd functions in a domain that includes a large part of the protocerebrum and a smaller part of the adjacent deuterocerebrum [20].
• An evolutionarily ancient gene, orthodenticle (otd), has a bcd-like role in the beetle Tribolium [21].
• Our results indicate that otd is a downstream target of the EGFR pathway during head development [16].
• We show that this effect is associated with otd repression of the homeotic selector gene Deformed (Dfd) [7].
• Repression of otd by runt does not require the conserved VVVRPY motif that mediates interaction between Runt and the co-repressor protein Groucho [8].

Analytical, diagnostic and therapeutic context of oc

• Targeting gene expression to the head: the Drosophila orthodenticle gene is a direct target of the Bicoid morphogen [22].
• Finally, as assayed by Einsteck transplantation assays, otd, like Xotx2, is able to respecify a tail/trunk organizer to a head organizer [23].
• A gel mobility shift assay reveals that a nuclear protein binds to the CAAT sequences present near the Otx binding sites in the enhancer region of Ars. The activation domain of HpOtxL resides in the C terminal region between amino acids 218 and 238 [24].

References