Disease relevance of Hoxa3

• We also show that the 2-kb promoter fragment is active in rhombomere 4 and in the ganglion of the cranial nerve complex VII/VIII that are devoid of Hoxa3 expression [1].

High impact information on Hoxa3

• A conserved DNA sequence common to these genes has been used to isolate a clone (Mo-10) from the mouse genome which contains a sequence coding for a protein domain that is homologous to the domain conserved in the Drosophila homeotic genes [2].
• Mo-10 has been mapped to the proximal portion of mouse chromosome 6, and its position in relationship to genes known to influence mouse morphogenesis is discussed [2].
• Here we show that the proteins encoded by the paralogous genes, Hoxa3 and Hoxd3, can carry out identical biological functions, and that the different roles attributed to these genes are the result of quantitative modulations in gene expression [3].
• The set of defects associated with the disruption of Hox-1.6 is distinct from and nonoverlapping with that of the closely linked Hox-1.5 gene [4].
• Using in situ hybridization, we show here that expression of the mouse homoeobox gene Mo-10 (ref. 7) is spatially restricted in the developing embryo and that localization of expression is already evident within the germ layers before their morphological differentiation [5].

Biological context of Hoxa3

• Regulatory comparisons of cis-elements from the chick and mouse Hoxa3 locus in both transgenic mouse and chick embryos have identified a conserved enhancer that mediates the late phase of Hoxa3 expression through a conserved auto/cross-regulatory loop [6].
• Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis [7].
• Both Hoxa-3 and Hoxa-3 proteins have a proline-rich region that contains consensus amino acid sequences for binding to Src homology 3 domains of some signal transduction proteins [8].
• We used Hoxa3 knockout mice and other mouse models to study the role of the fetal parathyroids in fetal calcium homeostasis [9].
• Homeobox gene Hoxa3 is strongly expressed in the third pharyngeal arch and pouch [10].

Anatomical context of Hoxa3

• Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms [6].
• In this study, we have compared the segmental expression and regulation of Hoxa3 and Hoxb3 in mouse and chick embryos to investigate how they are controlled after initial activation [6].
• The expression of the paralogous Hoxa3 and Hoxb3 genes extends from the posterior spinal cord up to the rhombomere (r) 4/5 boundary and both genes are upregulated specifically in r5 [11].
• Hoxa3 and pax1 transcription factors regulate the ability of fetal thymic epithelial cells to promote thymocyte development [12].
• Our results suggest that a Hoxa3-Pax1 genetic pathway is required for both epithelial cell growth and differentiation throughout thymus and parathyroid organogenesis [7].

Regulatory relationships of Hoxa3

• To examine the etiology of the regression of the third arch artery, we generated Hoxa3 homozygous null mutant embryos that expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the neural crest cells [13].

Other interactions of Hoxa3

• We found that the intergenic region between Hoxa3 and Hoxa4 contains several enhancers, which summed together mediate a pattern of expression closely resembling that of the endogenous Hoxa3 gene [11].
• In this study, we show that mutations in two transcription factors, Hoxa3 and Pax1, act synergistically to cause defective thymic epithelial cell development, resulting in thymic ectopia and hypoplasia [12].
• To investigate this problem, we have cloned and sequenced the intergenic region between Hoxa2 and Hoxa3 in the chick HoxA complex and used it for making comparative analyses with the respective human, mouse, and horn shark regions [14].
• We also studied Hoxa-3 mutants, but found no effect of this mutation on the cad6 expression pattern [15].
• Both the rate of placental calcium transfer and the plasma PTHrP level were normal in Hoxa3 mutants and their heterozygous siblings [9].

Analytical, diagnostic and therapeutic context of Hoxa3

• Paralogous Hox genes, such as Hoxa3, Hoxb3 and Hoxd3, generally have very similar patterns of expression, and gene targeting experiments have shown that members of paralogy group 3 can functionally compensate for each other [6].
• Furthermore, innervation of the carotid sinus and baroreceptor regions in the aortic arch and right subclavian artery were studied in the Hoxa3 null mutants having an abnormal carotid artery system by immunohistochemistry with TuJ1 and protein gene product (PGP) 9.5 antibodies, which recognize nerve fibers and neurons [16].
• These results indicate that Hoxa3 gene is crucial for the formation of the common carotid artery and the null mutant mice are the first useful animal models to show that the third arch arteries on both sides specifically degenerate but the fourth and sixth arch arteries are normal [16].

References