Homeotic gene

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Homeotic genes are genes which regulate the development of anatomical structures in various organisms such as echinoderms, [1] insects, mammals, and plants. Homeotic genes often encode transcription factor proteins, and these proteins affect development by regulating downstream gene networks involved in body patterning. [2]

Contents

Mutations in homeotic genes cause displaced body parts (homeosis), such as antennae growing at the posterior of the fly instead of at the head. [3] Mutations that lead to development of ectopic structures are usually lethal. [4]

Types

There are several subsets of homeotic genes. They include many of the Hox and ParaHox genes that are important for segmentation. [5] Hox genes are found in bilateral animals, including Drosophila (in which they were first discovered) and humans. Hox genes are a subset of the homeobox genes. The Hox genes are often conserved 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. [6] Both Hox and ParaHox are grouped as HOX-Like (HOXL) genes, a subset of the ANTP class (named after the Drosophila gene, Antennapedia). [7]

They also include the MADS-box-containing genes involved in the ABC model of flower development. [8] 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). [9]

Despite the 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 subset of homeotic genes.

Drosophila melanogaster

Homeotic selector gene complexes in the fruit fly Drosophila melanogaster Homeotic selector gene complexes.svg
Homeotic selector gene complexes in the fruit fly Drosophila melanogaster

One of the most commonly studied model organisms in regards to homeotic genes is the fruit fly Drosophila melanogaster . Its homeotic Hox genes occur in either the Antennapedia complex (ANT-C) or the Bithorax complex (BX-C) discovered by Edward B. Lewis. [10] Each of the complexes focuses on a different area of development. The antennapedia complex consists of five genes, including proboscipedia, and is involved in the development of the front of the embryo, forming the segments of the head and thorax. [11] The bithorax complex consists of three main genes and is involved in the development of the back of the embryo, namely the abdomen and the posterior segments of the thorax. [12]

During development (starting at the blastoderm stage of the embryo), these genes are constantly expressed to assign structures and roles to the different segments of the fly's body. [13] For Drosophila, these genes can be analyzed using the Flybase database.

Research

Much research has been done on homeotic genes in different organisms, ranging from basic understanding of how the molecules work to mutations to how homeotic genes affect the human body. Changing the expression levels of homeotic genes can negatively impact the organism. For example, in one study, a pathogenic phytoplasma caused homeotic genes in a flowering plant to either be significantly upregulated or downregulated. This led to severe phenotypic changes including dwarfing, defects in the pistils, hypopigmentation, and the development of leaf-like structures on most floral organs. [14] 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. [15] These studies, along with many others, show the importance of homeotic genes even after development.

See also

Related Research Articles

<span class="mw-page-title-main">Homeobox</span> DNA pattern affecting anatomy development

A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism.

<i>Drosophila</i> embryogenesis Embryogenesis of the fruit fly Drosophila, a popular model system

Drosophila embryogenesis, the process by which Drosophila embryos form, is a favorite model system for genetics and developmental biology. The study of its embryogenesis unlocked the century-long puzzle of how development was controlled, creating the field of evolutionary developmental biology. The small size, short generation time, and large brood size make it ideal for genetic studies. Transparent embryos facilitate developmental studies. Drosophila melanogaster was introduced into the field of genetic experiments by Thomas Hunt Morgan in 1909.

<span class="mw-page-title-main">Homeosis</span>

In evolutionary developmental biology, homeosis is the transformation of one organ into another, arising from mutation in or misexpression of certain developmentally critical genes, specifically homeotic genes. In animals, these developmental genes specifically control the development of organs on their anteroposterior axis. In plants, however, the developmental genes affected by homeosis may control anything from the development of a stamen or petals to the development of chlorophyll. Homeosis may be caused by mutations in Hox genes, found in animals, or others such as the MADS-box family in plants. Homeosis is a characteristic that has helped insects become as successful and diverse as they are.

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

<i>Antennapedia</i> Hox gene

Antennapedia is a Hox gene first discovered in Drosophila which controls the formation of legs during development. Loss-of-function mutations in the regulatory region of this gene result in the development of the second leg pair into ectopic antennae. By contrast gain-of-function alleles convert antennae into ectopic legs.

<span class="mw-page-title-main">CDX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The CDX2 protein is a homeobox transcription factor expressed in the nuclei of intestinal epithelial cells, playing an essential role in the development and function of the digestive system. CDX2 is part of the ParaHox gene cluster, a group of three highly conserved developmental genes present in most vertebrate species. Together with CDX1 and CDX4, CDX2 is one of three caudal-related genes in the human genome.

<span class="mw-page-title-main">PBX1</span> Protein found in humans

Pre-B-cell leukemia transcription factor 1 is a protein that in humans is encoded by the PBX1 gene. The homologous protein in Drosophila is known as extradenticle, and causes changes in embryonic development.

<span class="mw-page-title-main">HOXB6</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B6 is a protein that in humans is encoded by the HOXB6 gene.

<span class="mw-page-title-main">HOXB5</span> Protein-coding gene in humans

Homeobox protein Hox-B5 is a protein that in humans is encoded by the HOXB5 gene.

<span class="mw-page-title-main">HOXD11</span> Protein-coding gene in humans

Homeobox protein Hox-D11 is a protein that in humans is encoded by the HOXD11 gene.

<span class="mw-page-title-main">Homeobox protein goosecoid</span> Protein-coding gene in the species Homo sapiens

Homeobox protein goosecoid(GSC) is a homeobox protein that is encoded in humans by the GSC gene. Like other homeobox proteins, goosecoid functions as a transcription factor involved in morphogenesis. In Xenopus, GSC is thought to play a crucial role in the phenomenon of the Spemann-Mangold organizer. Through lineage tracing and timelapse microscopy, the effects of GSC on neighboring cell fates could be observed. In an experiment that injected cells with GSC and observed the effects of uninjected cells, GSC recruited neighboring uninjected cells in the dorsal blastopore lip of the Xenopus gastrula to form a twinned dorsal axis, suggesting that the goosecoid protein plays a role in the regulation and migration of cells during gastrulation.

<i>Bithorax</i> complex

The Bithorax complex (BX-C) is one of two Drosophila melanogaster homeotic gene complexes, located on the right arm of chromosome 3. It is responsible for the differentiation of the posterior two-thirds of the fly by the regulation of three genes within the complex: Ultrabithorax (Ubx), abdominal A (abd-A), and Abdominal B (Abd-B).

Homeotic selector genes confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation. Homeodomain proteins are transcription factors that share a DNA-binding domain called the homeodomain. Changes in the expression and function of homeotic genes are responsible for the changes in the morphology of the limbs of arthropods as well as in the axial skeletons of vertebrates. Mutations in homeotic selector genes do not lead to elimination of a segment or pattern, but instead cause the segment to develop incorrectly.

Zerknüllt is a gene in the Antennapedia complex of Drosophila and other insects, where it operates very differently from the canonical Hox genes in the same gene cluster. Comparison of Hox genes between species showed that the Zerknüllt gene evolved from one of the standard Hox genes in insects through accumulating many amino acid changes, changing expression pattern, losing ancestral function and gaining a new function.

M33 is a gene. It is a mammalian homologue of Drosophila Polycomb. It localises to euchromatin within interphase nuclei, but it is enriched within the centromeric heterochromatin of metaphase chromosomes. In mice, the official symbol of M33 gene styled Cbx2 and the official name chromobox 2 are maintained by the MGI. Also known as pc; MOD2. In human ortholog CBX2, synonyms CDCA6, M33, SRXY5 from orthology source HGNC. M33 was isolated by means of the structural similarity of its chromodomain. It contains a region of homology shared by Xenopus and Drosophila in the fifth exon. Polycomb genes in Drosophila mediate changes in higher-order chromatin structure to maintain the repressed state of developmentally regulated genes. It may also involved in the campomelic syndrome and neoplastic disorders linked to allele loss in this region. Disruption of the murine M33 gene, displayed posterior transformation of the sternal ribs and vertebral columns.

Michael Levine is an American developmental and cell biologist at Princeton University, where he is the Director of the Lewis-Sigler Institute for Integrative Genomics and a Professor of Molecular Biology.

The Cdx gene family, also called caudal genes, are a group of genes found in many animal genomes. Cdx genes contain a homeobox DNA sequence and code for proteins that act as transcription factors. The gene after which the gene family is named is the caudal or cad gene of the fruitfly Drosophila melanogaster. The human genome has three Cdx genes, called CDX1, CDX2 and CDX4. The zebrafish has no cdx2 gene, but two copies of cdx1 and one copy of cdx4. The Cdx gene in the nematode Caenorhabditis elegans is called pal-1.

<span class="mw-page-title-main">Hox genes in amphibians and reptiles</span>

Hox genes play a massive role in some amphibians and reptiles in their ability to regenerate lost limbs, especially HoxA and HoxD genes.

<span class="mw-page-title-main">CDX4 (gene)</span> Protein-coding gene in humans

Homeobox protein CDX-4 is a protein that in humans is encoded by the CDX4 gene. This gene is a member of the caudal-related homeobox transcription factor family that also includes CDX1 and CDX2.

Thomas Charles Kaufman is an American geneticist. He is known for his work on the zeste-white region of the Drosophila X chromosome. He is currently a Distinguished Professor of biology at Indiana University, where he conducts his current research on Homeotic Genes in evolution and development.

References

  1. ↑ Popodi E, et al. (1996). "Sea Urchin Hox Genes: Insights into the Ancestral Hox Cluster". Mol. Biol. Evol. 13 (8): 1078–1086. doi: 10.1093/oxfordjournals.molbev.a025670 . PMID   8865662.
  2. ↑ Hirth F, Hartmann B, Reichert H (May 1998). "Homeotic gene action in embryonic brain development of Drosophila". Development. 125 (9): 1579–89. doi:10.1242/dev.125.9.1579. PMID   9521896.
  3. ↑ Bürglin TR (2013). "Homeotic Mutation". Homeotic mutations. pp. 510–511. doi:10.1016/B978-0-12-374984-0.00727-0. ISBN   978-0-08-096156-9.{{cite book}}: |journal= ignored (help)
  4. ↑ 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. doi:10.1002/j.1460-2075.1994.tb06362.x. PMC   394922 . PMID   7907545.
  5. ↑ 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.
  6. ↑ 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. S2CID   9804218.
  7. ↑ Holland PW, Booth HA, Bruford EA (2007). "Classification and nomenclature of all human homeobox genes". BMC Biology. 5 (1): 47. doi: 10.1186/1741-7007-5-47 . PMC   2211742 . PMID   17963489.
  8. ↑ Theissen G (2001). "Development of floral organ identity: stories from the MADS house". Curr. Opin. Plant Biol. 4 (1): 75–85. Bibcode:2001COPB....4...75T. doi:10.1016/S1369-5266(00)00139-4. PMID   11163172.
  9. ↑ 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.
  10. ↑ Heuer JG, Kaufman TC (May 1992). "Homeotic genes have specific functional roles in the establishment of the Drosophila embryonic peripheral nervous system". Development. 115 (1): 35–47. doi:10.1242/dev.115.1.35. PMID   1353440.
  11. ↑ 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. doi:10.1242/dev.113.1.257. PMID   1684932.
  12. ↑ 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.
  13. ↑ 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 (1): 119–34. doi:10.1242/dev.117.1.119. PMID   7900984.
  14. ↑ 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 (6): 971–79. doi: 10.1111/j.1365-313X.2011.04650.x . PMID   21605209.
  15. ↑ 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 (10): 1465–71. doi:10.1136/gut.52.10.1465. PMC   1773830 . PMID   12970140.
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