Disease relevance of HOXA3

• BACKGROUND: Recent studies have suggested that susceptibility to chronic obstructive pulmonary disease (COPD) might be related to the length polymorphism of (GT)(n) repeat in the 5'-flanking region of heme oxygenase-1 (HOX-1) gene [1].

High impact information on HOXA3

• Skin cell cultures expressed the AIRE, Foxn1, and Hoxa3 transcription factors and a panel of autoantigens [2].
• Targeted overexpression of Hoxa3 in the rostral hindbrain led to the generation of ectopic somatic motoneurones in ventral rhombomeres 1-4, and was accompanied by the repression of the dorsoventral patterning gene Irx3 [3].
• Grafting of somites or retinoic acid-loaded beads beneath the rostral hindbrain induced the formation of somatic motoneurones in rhombomere 4 only, and Hox genes normally expressed more caudally (Hoxa3, Hoxd4) were induced in this region [3].
• In contrast, misdirecting of the neural crest by rostrocaudal rotation of r4 through r6 results in a reduction of Hoxa-3 expression in the third branchial arch and corresponding deficits in third arch-derived structures of the hyoid apparatus [4].
• Together these findings illustrate how the morphoregulatory protein, HOXA3 can facilitate tissue remodeling via coordinated changes in both epithelial and endothelial cell gene expression and behavior in adult tissues during wound repair [5].

Biological context of HOXA3

• The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5 [6].
• HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair [5].
• Given the presence of an AP-1 site in HOX-1 promoter region, the activity of AP1 transcription factor was examined [7].
• Hoxa3 mutant homozygotes have defects in the development of all three organs [8].
• In the current studies, we sequenced and characterized the gene for the homeodomain protein (hox1) in a bipolar mushroom, Pholiota nameko, which is a putative homologue of A mating type genes in the tetrapolar basidiomycete, Coprinopsis cinerea [9].

Anatomical context of HOXA3

• In addition, we show that HOXA3 promotes migration of endothelial cells and keratinocytes in a uPAR-dependent manner [5].
• Further, the observed defects in thymus development may be mediated by RA-induced alterations in the expression of Hoxa3 [10].
• The thyroid defects seen in Hoxa3 single mutants are exacerbated in double mutants with either of its paralogs, although none of the double-mutant combinations resulted in thyroid agenesis [8].
• Somatic motoneurone specification in the hindbrain: the influence of somite-derived signals, retinoic acid and Hoxa3 [3].
• When analogous ablations are performed at the 10-12 somite stage, however, a marked increase in the numbers of DiI/Hoxa-3-positive cells from r7 are observed within the third branchial arch [4].

Associations of HOXA3 with chemical compounds

• HOX-1 mRNA levels were found to be maximally induced after 6h of treatment with 200muM H(2)O(2) and remained elevated for at least 24h [7].

Other interactions of HOXA3

• We find that after exchange of first and third arch crest by rotation of r1-7, crest alters its expression of hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the reestablishment of the normal branchial arch Hox code [11].

Analytical, diagnostic and therapeutic context of HOXA3

• Identification and linkage mapping of the genes for the putative homeodomain protein (hox1) and the putative pheromone receptor protein homologue (rcb1) in a bipolar basidiomycete, Pholiota nameko [9].

References