In vertebrates, the genes encoding the class oftranscription factors calledhomeobox genes are found inclusters named A, B, C, and D on four separatechromosomes. Expression of these proteins is spatially and temporally regulated duringembryonic development. This gene is part of the A cluster onchromosome 7 and encodes a DNA-binding transcription factor which may regulategene expression,morphogenesis, and differentiation. Three transcript variants encoding two different isoforms have been found for this gene.[7]
During normalfetal development, HoxA3 is expressed inmesenchymalneural crest cells andendodermal cells found in thethird pharyngeal pouch.[8] Expression of HoxA3 in these cells affects the proper formation of thethymus,thyroid, andparathyroid organs.[9][10] While the gene does not seem to affect the proliferation or migration of the pharyngeal neural crest cells, it does appear to triggercellular differentiation events required to form these organs.[9] Knockout of HoxA3 leads to failure in forming the thymus (athymia) and parathyroid gland (aparthyroidism).[10] Mutant HoxA3 also causes a reduction in thyroid size. While thefollicular andparafollicular cells still differentiate, their numbers are reduced and they are not evenly distributed throughout the gland.[9] Mutant HoxA3 models show similarphenotypes as those seen inDiGeorge's syndrome, and it is possible that the two are linked.[9]
^abcdManley NR, Capecchi MR (July 1995). "The role of Hoxa-3 in mouse thymus and thyroid development".Development.121 (7):1989–2003.doi:10.1242/dev.121.7.1989.PMID7635047.
Mulder GB, Manley N, Maggio-Price L (December 1998). "Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1".Teratology.58 (6):263–75.doi:10.1002/(SICI)1096-9926(199812)58:6<263::AID-TERA8>3.0.CO;2-A.PMID9894676.
Kosaki K, Kosaki R, Suzuki T, Yoshihashi H, Takahashi T, Sasaki K, et al. (February 2002). "Complete mutation analysis panel of the 39 human HOX genes".Teratology.65 (2):50–62.doi:10.1002/tera.10009.PMID11857506.
Kim J, Bhinge AA, Morgan XC, Iyer VR (January 2005). "Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment".Nature Methods.2 (1):47–53.doi:10.1038/nmeth726.PMID15782160.S2CID6135437.
