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The dachshund gene (dac) was found in Drosophila as a mutation that results in shorter legs. Dac was later found to be an important developmental gene in Drosophila, responsible for proper leg, eye, retinal and gonadal development.[1] Dac encodes a nuclear protein which is similar to the Sno/Ski co-repressor protein family.[2] The dac protein is a transcription factor and is part of the Retinal Determination Gene Network (RDGN), a group of transcription factors that regulate the development of the eye and other tissues.[3] It effects the expression of the other genes in the RDGN but dac's expression can also be effected by the RDGN genes.[3]
The dac gene is highly conserved from Drosophila to humans;[2] DACH1 and DACH2 are the human homologues .[2] In humans, the DACH genes are tumor suppressor genes.[2]
Roles in Development
[edit]The dac gene is important for development. New-born mice with non-functioning (or knocked out) DACH1 or both DACH1 and DACH2 knocked out genes die within two days.[2][4] DACH1 knockout mice die after birth but do not appear to have any physical defects.[4] This may be due to the fact that DACH1 and DACH2 function in the same way, so they are functionally redundant,[2] a common trait in important developmental genes.[5]
Role in Gonadal Development
[edit]In Drosophila, dac required for proper development of the female reproductive system, in particular the Müllerian duct.[2] It is expressed in a way that is specific to each sex, helping to patterning of male and female genitalia.[2] In males, dac expression is reduced by the wingless (wg) gene but the decapentaplegic (dpp) gene enhances dac expression. Where in female flies, wg enhances dac expression and dpp reduces it. This is possible because of differential splicing of the protein sexless (sxl).[2]
Role in Eye Development
[edit]In Drosophila, dac is an important gene in the development of the eye. It is part of the Retinal Determination Gene Network, a group of core genes that are essential for eye development.[3] It is required for the development of the photoreceptor cells, which make up part of the ommatidia. Dac has many molecular interactions and most of them are not well known. It can repress and enhance expression of other genes and it can act independently or as a complex.[3]
During development, Dac is expressed in the preproneural region and the morphogenic furrow regions of the eye disc.[3] It is regulated by dpp and epidermal growth factor receptor (EGFR).[3]
Dac can inhibit the Yorkie-Homothorax complex, a transcription factor that promotes the transcription of cell proliferation proteins, on multiple levels.[3] By inhibiting this complex, dac is controlling the tissue growth during eye development. Dac is a tumor suppressor gene because of this ability to inhibit and control tissue growth.
Role in Leg Development
[edit]The Drosophila embryonic leg development depends on the dac gene. Mutations in the dac gene leads to shortened legs that are missing the intermediate segments of the leg.[6] Leg development is initiated by dpp and wg turning on the distal-less (Dll) gene, which in turn activates the dac gene.[7] This is important for creating the Proximal-Distal axis, which is essential for limb formation.
References
[edit]- ^ Kumar, J. P. (2001-11-01). "Signalling pathways in Drosophila and vertebrate retinal development". Nature Reviews. Genetics. 2 (11): 846–857. doi:10.1038/35098564. ISSN 1471-0056. PMID 11715040.
- ^ a b c d e f g h i Popov, Vladimir M.; Wu, Kongming; Zhou, Jie; Powell, Michael J.; Mardon, Graeme; Wang, Chenguang; Pestell, Richard G. (2010-01-01). "The Dachshund gene in development and hormone-responsive tumorigenesis". Trends in endocrinology and metabolism: TEM. 21 (1): 41–49. doi:10.1016/j.tem.2009.08.002. ISSN 1879-3061. PMC 2818438. PMID 19896866.
- ^ a b c d e f g Silver, Serena J.; Rebay, Ilaria (2005-01-01). "Signaling circuitries in development: insights from the retinal determination gene network". Development. 132 (1): 3–13. doi:10.1242/dev.01539. ISSN 0950-1991. PMID 15590745.
- ^ a b Hanson, Isabel M (2001-12-01). "Mammalian homologues of the Drosophila eye specification genes". Seminars in Cell & Developmental Biology. 12 (6): 475–484. doi:10.1006/scdb.2001.0271.
- ^ Rudel, David; Sommer, Ralf J (2003-12-01). "The evolution of developmental mechanisms". Developmental Biology. 264 (1): 15–37. doi:10.1016/S0012-1606(03)00353-1.
- ^ Mardon, G.; Solomon, N. M.; Rubin, G. M. (1994-12-01). "dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila". Development (Cambridge, England). 120 (12): 3473–3486. ISSN 0950-1991. PMID 7821215.
- ^ Estella, Carlos; Voutev, Roumen; Mann, Richard S. (2012-01-01). "A Dynamic Network of Morphogens and Transcription Factors Patterns the Fly Leg". Current topics in developmental biology. 98: 173–198. doi:10.1016/B978-0-12-386499-4.00007-0. ISSN 0070-2153. PMC 3918458. PMID 22305163.
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