Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the DMRT1 gene. [5] [6] [7]
Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the DMRT1 gene. [5] [6] [7]
DMRT1 is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cells. The DMRT1 gene is located at the end of the 9th chromosome. This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes, and is found to be the key sex-determining factor in chickens. [8] The majority of DMRT1 protein is located in the testicular cord and Sertoli cells, with a small amount in the germ cells.
Defective testicular development and XY feminization occur when this gene is hemizygous. [5] Two copies of the DMRT1 gene are required for normal sexual development. When a DMRT1 gene is lost, the most common disease is chromosome 9p deletion, which causes abnormal testicular formation and feminization. The DMRT1 gene is critical for male sex determination; without this gene the female characteristic takes over and male characteristic is slight or non-existent.
When DMRT1 is knocked out in mice, the mice showed changes in both Sertoli and germ cells soon after formation of the gonadal ridge. The main defects associated with DMRT1 knockout were developmental arrest, excess proliferation of germ cells, and failure to undergo meiosis, mitosis, or migration. Thus, the knockout model shows that loss of the DMRT1 gene is associated with incomplete germ cell development leading to infertility, abnormal testicular formation, and/or feminization of the affected individual.[ citation needed ] Induced knockout of DMRT1 in adult male mice has been found to cause transdifferentiation of somatic cells in the testis to the equivalent cell types that would ordinarily be found in the ovary. [9] Conversely, conditional expression of DMRT1 in the gonad of female mice caused the apparent transdifferentiation of ovarian somatic (granulosa) cells to the equivalent cell type (Sertoli) ordinarily found in males. [10]
A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.
Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.
The male reproductive system consists of a number of sex organs that play a role in the process of human reproduction. These organs are located on the outside of the body, and within the pelvis.
The genital ridge is the precursor to the gonads. The genital ridge initially consists mainly of mesenchyme and cells of underlying mesonephric origin. Once oogonia enter this area they attempt to associate with these somatic cells. Development proceeds and the oogonia become fully surrounded by a layer of cells.
The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling the activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered.
The germ cell nuclear factor (GCNF), also known as RTR or NR6A1, is a protein that in humans is encoded by the NR6A1 gene. GCNF is a member of the nuclear receptor family of intracellular transcription factors.
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In molecular biology the DM domain is a protein domain first discovered in the doublesex proteins of Drosophila melanogaster and is also seen in C. elegans and mammalian proteins. In D. melanogaster the doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. These proteins are believed to function as transcription factors on downstream sex-determination genes, especially on neuroblast differentiation and yolk protein genes transcription.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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