Disease relevance of ur

• WT1 is a tumor suppressor gene with a key role in urogenital development and the pathogenesis of Wilms' tumor [1].
• Rara(-/-) Rarb2(-/-) mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret [2].
• Aldh1a2 haploinsufficiency prevents the appearance of spina bifida and rescues the development of posterior structures (sacral/caudal vertebrae, hindgut, urogenital tract), while partly preventing cervical vertebral transformations and hindbrain pattern alterations in Cyp26a1(-/-) mice [3].
• Spina bifida and truncation of the tail and lumbosacral region (including abnormalities of the kidneys, urogenital tract, and hindgut) are the most conspicuous defects, leading in extreme cases to a sirenomelia ("mermaid tail") phenotype [4].
• Characteristic associated anomalies include ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation [5].

High impact information on ur

• Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder [2].
• During embryogenesis, Sox9 is expressed in all cartilage primordia and cartilages, coincident with the expression of the collagen alpha1(II) gene (Col2a1) . Sox9 is also expressed in other tissues, including the central nervous and urogenital systems [6].
• The Wilms' tumour suppressor gene 1 (WT1) (1,2) encodes four C2H2 zinc finger-containing proteins (3) critical for normal mammalian urogenital development (4) [7].
• The linear transcript was not detected in any other fetal tissue nor in any adult tissue tested, and was expressed only in the genital ridge portion of the urogenital ridge [8].
• In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations [9].

Chemical compound and disease context of ur

• Both retinoid receptor null mutants and classic nutritional deficiency studies have demonstrated that retinoids are essential for the normal development of diverse embryonic structures (e.g. eye, heart, nervous system, urogenital tract) [10].
• Naturally occurring mutations in the gene encoding 5 alpha-reductase type 2 cause male pseudohermaphroditism, indicating that this isozyme is responsible for the synthesis of dihydrotestosterone required for virilization of the embryonic male urogenital tract [11].
• Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from Urogenital Chlamydia muridarum Infection [12].
• Virilization of urogenital sinus is also androgen-dependent [13].
• Since previous literature suggested that estrogen-treated male mice are models for human benign prostatic hypertrophy, a series of studies was designed to examine urine retention and urogenital tract changes in rodents given chronic estradiol-17 beta (E) and dihydrotestosterone (DHT) treatments [14].

Biological context of ur

• We have screened an 11.5 day post coitum urogenital ridge cDNA library with an oligonucleotide encoding a sequence conserved between a variety of zinc finger proteins [15].
• Villin gene expression is strictly regulated during adult life and embryonic development in the digestive and urogenital tracts and, thus, may be used as a marker of the digestive and renal cell lineages [16].
• In order to identify additional sex-determining or gonadal differentiation genes we have examined gene expression in the developing gonads of the mouse using cDNA microarrays constructed from a normalized urogenital ridge library [17].
• The rescuing YAC did not display appropriate urogenital expression of Gata2, implying the existence of a urogenital-specific enhancer(s) lying outside the boundaries of this transgene [18].
• Multiple, distant Gata2 enhancers specify temporally and tissue-specific patterning in the developing urogenital system [18].

Anatomical context of ur

• During mammalian embryonic development, the ovaries and testes develop from somatic cells of the urogenital ridges as indifferent gonads, harbouring primordial germ cells that have migrated there [19].
• This approach may represent a means of preventing recurrent and acute infections of the urogenital mucosa [20].
• Epithelial-mesenchymal interactions in prostatic development. I. morphological observations of prostatic induction by urogenital sinus mesenchyme in epithelium of the adult rodent urinary bladder [21].
• Epithelial-mesenchymal interactions in prostatic development. II. Biochemical observations of prostatic induction by urogenital sinus mesenchyme in epithelium of the adult rodent urinary bladder [22].
• During embryo-genesis A-myb is predominantly expressed in several regions of the developing central nervous system (CNS) and the urogenital ridge [23].

Associations of ur with chemical compounds

• Immunohistochemistry analysis of murine prostate development demonstrated epithelial expression of CSF-1R during the protrusion of prostatic buds from the urogenital sinus, during the prepubertal and androgen-driven proliferative expansion and branching of the gland, with a decline in older animals [24].
• Adenosis occurred in transplanted C57BL and BALB/c mice Müllerian-derived reproductive tract regions, cervix, and/or fornix (FX), and middle vagina but never in the urogenital sinus-derived portion of the vagina, after a 1-mo exposure to endogenous ovarian hormones or exogenous estradiol (E2) [25].
• BPH-1 cells were induced to form tumors either by recombination with human prostatic carcinoma-associated fibroblasts (CAFs) or by exposure to carcinogenic doses of testosterone and estradiol (T+E2) after recombination with rat urogenital sinus mesenchyme [26].
• Of the urogenital tumors induced by arsenic plus diethylstilbestrol, 80% were malignant, and 55% were multiple site [27].
• As such, the tumor line will serve as a useful model for studying sex steroid-responsive cells of the urogenital epithelium [28].

Physical interactions of ur

• There was substantial atrophy of the urogenital complex and significantly (P < 0.0005) reduced levels of testosterone-dependent testicular relaxin-like factor mRNA expression [29].

Regulatory relationships of ur

• BMP7 is expressed in the periurethral urogenital mesenchyme prior to formation of the prostate buds and, subsequently, in the prostate epithelium [30].
• At later stages, Lbx2 transcripts are expressed in the brain and organs derived from the urogenital ridge, including the gonadal tubercle, kidneys, and adrenal glands [31].
• At the onset of ductal morphogenesis in the developing prostate, Shh expression condenses at evaginations of urogenital sinus epithelium and activates Gli transcription factors in the adjacent mesenchyme [32].
• At the same time, Emx2 is expressed in the epithelial components of the developing urogenital system and, in Emx2 mutant mice, the kidneys, ureters, gonads and genital tracts were completely missing [33].
• The Bmp4 gene was most highly expressed in the male urogenital sinus from embryonic day 14 through birth, a period marked by formation of main prostatic ducts and initiation of ductal branching [34].

Other interactions of ur

• Here we show that transcripts of the LIM homeobox gene Lhx9 are present in urogenital ridges of mice at embryonic day 9.5; later they localize to the interstitial region as morphological differentiation occurs [19].
• The gonads of Pod1 knockout (KO) mice were markedly hypoplastic, and the urogenital tracts of both XX and XY mice remained indistinguishable throughout embryogenesis [35].
• PPARgamma and PBP expression overlapped in the brown fat and urogenital sinus at stage E15.5 of embryogenesis, whereas SRC-1 expression occurred mostly in neuroepithelium and cartilage between stages E9.5 and E13.5 of embryogenesis [36].
• Nonetheless, the chemical inhibitor of Shh signaling, cyclopamine, produced a graded inhibition of Gli gene expression (Gli1>Gli2>Gli3) in urogenital sinus explants that was paralleled by a severe inhibition of ductal budding [37].
• The addition of Gdnf protein to urogenital tracts taken from Gdf11 null embryos induced ectopic ureteric bud formation along the Wolffian duct [38].

Analytical, diagnostic and therapeutic context of ur

• Importantly, our urogenital sinus transplantation studies demonstrate that p63 prevents intestinal differentiation of the urogenital sinus endoderm and is therefore required to maintain commitment to the prostate cell lineage [39].
• Furthermore, in situ hybridization shows that this region coincides with the anterior limit of embryonic Hoxa-10 expression in the urogenital ducts and a parallel transformation is observed in Hoxa-10 mutant males at the junction of the epididymis and ductus deferens [40].
• For both diets, the urogenital wet weights and lymph node wet weights in the 20-mg/kg treatment groups were significantly lower as compared to vehicle control groups [41].
• The ontogeny of Müllerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge [42].
• Cell cultures from the urogenital ridge have been established to facilitate the study of the regulation and downstream interactions of Sry in mammalian sex determination [43].

References