Homeotic genes are genes which regulate the development of anatomical structures in various organisms such as insects, mammals, and plants. This regulation is done via the programming of various transcription factors by the homeotic genes, and these factors affect genes through regulatory genetic pathways.
Mutations in the homeotic genes can occur, leading to what are known as homeotic mutants. These mutants display ectopic placement of body parts (such as antennae growing at the posterior of the fly instead of at the head) or abnormal expression of the homeotic gene. Mutations that lead to these ectopic placements are usually lethal to the organism.
Types of Homeotic Genes
There are several subsets of homeotic genes. They include many of the Hox and ParaHox genes which are important for segmentation, Hox genes (also known as homeobox genes) are found in countless organisms including Drosophila (in which they were first discovered), vertebrates, and mammals, including humans. The Hox genes are often preserved across species, so some of the Hox genes of Drosophila are homologous to those in humans. In general, Hox genes play a role of regulating expression of genes as well as aiding in development and assignment of specific structures during embryonic growth. This can range from segmentation in Drosophila to central nervous system (CNS) development in vertebrates.
They also include the MADS-box-containing genes involved in the ABC model of flower development. Besides flower-producing plants, the MADS-box motif is also present in other organisms such as insects, yeasts, and mammals. They have various functions depending on the organism including flower development, proto-oncogene transcription, and gene regulation in specific cells (such as muscle cells). Despite terms being commonly interchanged, not all homeotic genes are Hox genes; the MADS- box genes are homeotic but not Hox genes. Thus, the Hox genes are a proper subset of homeotic genes.
Drosophila melanogaster Homeotic Genes
One of the most commonly studied model organisms in regards to homeotic genes is Drosophila, specifically Drosophila melanogaster. The homeotic genes of this organism occur in either the Antennapedia complex (ANT-C) or the Bithorax complex (BX-C). Each of the complexes focuses on a different area of development. The antennapedia complex is composed of five genes, including proboscipedia, and is involved in the development of the upper area of the fly such as the head and the thorax segments. The bithorax complex is composed of three main genes and is involved in the development of the lower area of the fly such as the abdominal area as well as the posterior segments and thorax. 
During development (starting at the blastoderm stage of the embryo), these genes are constantly expressed in order give the different segments of the fly body specific structures and roles. For Drosophila, these genes can be analyzed using the Flybase database.
Homeotic Gene Research
Much research has been done on homeotic genes, ranging from basic understanding of how the molecules work to mutations to how homeotic genes affect the human body. Multiple model organisms are used even though Drosophila is the most common.
More current research has shown how changing the expression levels of homeotic genes can negatively impact the organism. For example, in one study, a pathogenic phytoplasma caused homeotic genes to either be significantly upregulated or downregulated. This led to severe phenotypic changes including dwarf phenotypes, defects in the pistils, hypopigmentation, and the development of leaf-like structures on most floral organs. In another study, it was found that the homeotic gene Cdx2 acts as a tumor suppressor. In normal expression levels, the gene prevents tumorgenesis and colorectal cancer when exposed to carcinogens; however, when Cdx2 was not well expressed, carcinogens caused tumor development. These studies along with many others show the importance of homeotic genes even after development.
- Hirth F, Hartmann B, Reichert H (May 1998). "Homeotic gene action in embryonic brain development of Drosophila". Development 125: 1579–89. PMID 9521896.
- Andrew DJ, Horner MA, Petitt MG, et al. (March 1, 1994). "Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes". EMBO Journal 13 (5): 1132–44. PMC 394922. PMID 7907545.
- Young T, Rowland JE, van de Ven C, et al. (October 2009). "Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos". Dev. Cell 17 (4): 516–26. doi:10.1016/j.devcel.2009.08.010. PMID 19853565.
- Akin ZN, Nazarali AJ (2005). "Hox Genes and Their Candidate Downstream Targets in the Developing Central Nervous System". Cellular and Molecular Neurobiology 25 (3-4): 697–741. doi:10.1007/s10571-005-3971-9. PMID 16075387.
- Theissen G (2001). "Development of floral organ identity: stories from the MADS house". Curr. Opin. Plant Biol. 4 (1): 75–85. doi:10.1016/S1369-5266(00)00139-4. PMID 11163172.
- Shore P, Sharrocks AD (1995). "The MADS-box family of transcription factors". European Journal of Biochemistry 229 (1): 1–13. doi:10.1111/j.1432-1033.1995.0001l.x. PMID 7744019.
- Heuer JG, Kaufman TC (May 1992). "Homeotic genes have specific functional roles in the establishment of the Drosophila embryonic peripheral nervous system". Development 115: 35–47. PMID 1353440.
- Randazzo FM, Cribbs DL, Kaufman TC (Sep 1991). "Rescue and regulation of proboscipedia: a homeotic gene of the Antennapedia Complex". Development 113 (1): 257–71. PMID 1684932.
- Maeda RK, Karch F (Apr 2006). "The ABC of the BX-C: the bithorax complex explained". Development 133 (8): 1413–22. doi:10.1242/dev.02323. PMID 16556913.
- Breen TR, Harte PJ (January 1993). "trithorax regulates multiple homeotic genes in the bithorax and Antennapedia complexes and exerts different tissue-specific, parasegment-specific and promoter-specific effects on each". Development 117: 119–34. PMID 7900984.
- Himeno M, Neriya Y, et al. (July 1, 2011). "Unique morphological changes in plant pathogenic phytoplasma-infected petunia flowers are related to transcriptional regulation of floral homeotic genes in an organ-specific manner". The Plant Journal 67: 971–79. doi:10.1111/j.1365-313X.2011.04650.x. PMID 21605209.
- Bonhomme C, Duluc I, et al. (October 2003). "The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development". Gut 52: 1465–71. doi:10.1136/gut.52.10.1465. PMID 12970140.