High impact information on exd

• MEIS1 is able to rescue hth mutant phenotypes and can induce the cytoplasmic-to-nuclear translocation of EXD in cell culture and Drosophila embryos [1].
• Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx [2].
• We further show that extradenticle modulates the DNA binding activity of engrailed to a different target site [3].
• Thus, the ability of different homeotic genes to specify distinct segmental patterns may depend on cooperative interactions with proteins such as exd that selectively modulate their otherwise similar DNA binding specificities [4].
• However, most of the cooperative interactions arise from the YPWM amino-acid motif of Ultrabithorax-located amino-terminally to its homeodomain-which forms a reverse turn and inserts into a hydrophobic pocket on the Extradenticle homeodomain surface [5].

Biological context of exd

• Here we show that the PNS phenotype of exd mutant embryos is virtually indistinguishable from that of hth mutant embryos and does not simply follow the homeotic transformations observed in the epidermis [6].
• Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites [7].
• The spatial distribution of the HTH protein during embryonic development is very similar to the distribution of the Extradenticle (EXD) protein, a known modulator of homeotic gene activity [6].
• Transcriptional activation by extradenticle in the Drosophila visceral mesoderm [8].
• A 420 bp element from dpp contains EXD binding sites necessary for expressing a reporter gene in both these locations [8].

Anatomical context of exd

• Regulation and function of Scr, exd, and hth in the Drosophila salivary gland [9].
• Patterning function of homothorax/extradenticle in the thorax of Drosophila [10].
• Moreover, exd is also required for functions normally not associated with homeosis, such as the maintenance of the dorsoventral pattern, the specification of subpatterns in adult appendages or the arrangement of bristles in the mesonotum and genitalia [11].
• Consistent with this interpretation, the proximal determinant extradenticle (exd) was present in cell nuclei all of the way to the tip of the sawfly proleg, whereas it was not detectable in the nuclei of cells near the tip of the lepidopteran proleg [12].
• Furthermore, the nuclear import of Exd correlates with the transcription of an exd-dependent reporter gene in the endoderm [13].

Associations of exd with chemical compounds

• The activity of this NES is inhibited by the antibiotic Leptomycin B, suggesting that Exd is exported by a CRM1/exportin1-related export pathway [14].
• This hypoactive form of ANTP, but not the alanine-substituted form, is also reduced in its ability to bind to DNA cooperatively with the homeodomain protein Extradenticle [15].
• Two tryptophan residues present in the Drosophila and murine Engrailed EH2 domain are required for cooperativity with extradenticle and Pbx, respectively [16].
• HTH binds to DNA as part of a HTH/Hox/EXD trimeric complex, and we show that this complex is essential for the activation of a natural Hox target enhancer [17].

Physical interactions of exd

• HTH binds to the homeotic cofactor Extradenticle (EXD) and translocates it to the nucleus [18].
• We also provide evidence that Ubx and exd bind to neighboring sites on this DNA and interact directly to stabilize the DNA-bound form of Ubx [4].
• Interestingly, we found that the activity of the enhancer is only stimulated by DPP signaling significantly upon binding of LAB and EXD [19].
• First, we provide evidence that the Hox protein Deformed (Dfd) can interact with simple DNA-binding sites in Drosophila embryos in the absence of Exd, but this binding is not sufficient for transcriptional activation of reporter genes [20].
• The Deformed binding sites do not have the consensus sequence for cooperative binding with the cofactor Extradenticle, and we do not detect cooperative binding to these sites, though we cannot rule out an independent role for Extradenticle [21].
• Together with previous reports, this finding highlights that the Hox protein Ubx has multiple ways to interact with the Exd cofactor and suggests that flexibility in Hox-PBC contacts contributes to specify and diversify Hox protein function [22].

Other interactions of exd

• Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein [1].
• Activation does not require Ubx, demonstrating that EXD can activate transcription independently of homeotic proteins [8].
• First, removing the function of exd or hth, which is required for the nuclear localization of Exd protein, transforms the antenna into leg; such transformations occur without activation of Antp [23].
• However, in thoracic segments, Exd is required for repression (as well as activation) by En [24].
• In the proximal domain, exd activity prevents cells from responding to Dpp and Wg [25].

Analytical, diagnostic and therapeutic context of exd

• Immunocytochemistry has been used to investigate whether the co-repressor Groucho (Gro; vertebrate homolog: TLE) and the co-factor Extradenticle (Exd; vertebrate homolog: Pbx) are expressed in the cercal system [26].

References