NCBI Summary:
This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]
General function
Cytoskeleton
Comment
Cellular localization
Cytoskeleton
Comment
Ovarian function
Comment
Novel action of FOXL2 as mediator of Col1a2 gene autoregulation. Marongiu M et al. (2016) FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause.//////////////////
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-? signalling during follicle development in the mare. da Silveira JC et al. (2015) Age-related decline in fertility is a consequence of low oocyte number and/or low oocyte competence resulting in pregnancy failure. Transforming growth factor (TGF)-β signalling is a well-studied pathway involved in follicular development and ovulation. Recently, small non-coding RNAs, namely microRNAs (miRNAs), have been demonstrated to regulate several members of this pathway; miRNAs are secreted inside small cell-secreted vesicles called exosomes. The overall goal of the present study was to determine whether altered exosome miRNA content in follicular fluid from old mares is associated with changes in TGF-β signalling in granulosa cells during follicle development. Follicular fluid was collected at deviation (n = 6), mid-oestrus (n = 6) and preovulation (n = 6) for identification of exosomal miRNAs from young (3-12 years) and old (20-26 years) mares. Analysis of selected TGF-β signalling members revealed significantly increased levels of interleukin 6 (IL6) in granulosa cells from mid-oestrus compared with preovulatory follicles, and collagen alpha-2(I) chain (COL1A2) in granulosa cells from deviation compared with preovulatory follicles in young mares. In addition, granulosa cells from old mares had significantly altered levels of DNA-binding protein inhibitor ID-2 (ID2), signal transducer and activator of transcription 1 (STAT1) and cell division cycle 25A (CDC25A). Finally, changes in exosomal miRNA predicted to target selected TGF-β members were identified.//////////////////