| folliculogenesis specific bHLH transcription factor | OKDB#: 1675 |
| Symbols: | FIGLA | Species: | human | ||
| Synonyms: | POF6, BHLHC8, FIGALPHA | Locus: | 2p13.3 in Homo sapiens |
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| General Comment |
Reconstitution of the oocyte transcriptional network with transcription factors. Hamazaki N et al. (2020) During female germline development, oocytes become a highly specialized cell type and form a maternal cytoplasmic store of crucial factors. Oocyte growth is triggered at the transition from primordial to primary follicle and is accompanied by dynamic changes in gene expression1, but the gene regulatory network that controls oocyte growth remains unknown. Here we identify a set of transcription factors that are sufficient to trigger oocyte growth. By investigation of the changes in gene expression and functional screening using an in vitro mouse oocyte development system, we identified eight transcription factors, each of which was essential for the transition from primordial to primary follicle. Notably, enforced expression of these transcription factors swiftly converted pluripotent stem cells into oocyte-like cells that were competent for fertilization and subsequent cleavage. These transcription-factor-induced oocyte-like cells were formed without specification of primordial germ cells, epigenetic reprogramming or meiosis, and demonstrate that oocyte growth and lineage-specific de novo DNA methylation are separable from the preceding epigenetic reprogramming in primordial germ cells. This study identifies a core set of transcription factors for orchestrating oocyte growth, and provides an alternative source of ooplasm, which is a unique material for reproductive biology and medicine.//////////////////
Huntriss J, et al reported the isolation, characterization and expression of the human Factor In the Germline alpha (FIGLA) gene in ovarian follicles and oocytes.
The Factor In the Germline alpha (FIGalpha) transcription factor regulates expression of the zona pellucida proteins ZP1, ZP2 and ZP3 and is essential for folliculogenesis in the mouse. Using the published mouse Figla sequence, BLAST searches identified a human chromosome 2 BAC clone with high sequence identity. Using PCR primers derived from this clone, amplicons derived from ovarian follicles and mature oocytes revealed 100% identity with the appropriate human BAC clone, the expected homology with the mouse Figla gene sequence, and homology on translation with the FIGalpha protein identified in the Japanese rice fish, medaka (Oryzias latipes). PCR expression profiling of this transcript revealed FIGLA mRNA expression in cDNA derived from ovarian follicles (5/5 samples from the primordial through to the secondary stage) mature oocytes (6/9 samples), and less frequently in preimplantation embryos (2/7 samples). Subsequent BLAST searches revealed the predicted full length coding sequence of the human FIGalpha protein which demonstrates 68 and 25% similarity overall to mouse and medaka proteins respectively, with 96 and 57% identity respectively within the basic helix-loop-helix region. This confirms our identification of the human homologue for this gene which maps to chromosome 2p12. Further work is required to understand its role in normal human oocyte development and the potential involvement in human infertility.
NCBI Summary: This gene encodes a protein that functions in postnatal oocyte-specific gene expression. The protein is a basic helix-loop-helix transcription factor that regulates multiple oocyte-specific genes, including genes involved in folliculogenesis and those that encode the zona pellucida. Mutations in this gene cause premature ovarian failure type 6. [provided by RefSeq, Sep 2009] |
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| General function | DNA binding, Transcription factor | ||||
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| Cellular localization | Nuclear | ||||
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| Ovarian function | Follicle endowment, Initiation of primordial follicle growth, Oogenesis | ||||
| Comment | Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary. Bayne RA,et al 2004 . The process of primordial follicle formation is central to the determination of a woman's reproductive lifespan, and in humans occurs towards the end of mid-gestation. Gene knockout analysis in the mouse has shown that Figla, a transcription factor specifically expressed in germ cells, is essential for oocytes to survive and form primordial follicles. Our objective was to investigate whether a human homologue present in the genome database plays a similar role in human ovary development. Standard and real-time RT-PCR demonstrated that the human FIGLA gene is expressed in the fetal ovary but not by a range of other tissues, and that expression increases across mid-gestation, rising some 40-fold by the time of primordial follicle formation. The entire coding sequence was cloned and new exonic sequences identified. Electrophoretic mobility shift assays with in vitro-expressed human FIGLA protein showed that, as in the mouse, FIGLA can heterodimerize with E12 protein and bind to the E-box of the human ZP2 promoter. Similar mobility shifts were identified in human fetal ovary extracts. These results suggest that FIGLA is involved in continued oocyte survival as primordial follicles form in the human as in the rodent ovary.//////////A Lentiviral Vector Visualizing the Germ Cell Specification In Vitro Under the Control of Figla Promoter. Chu Z et al. (2015) Premature ovarian failure (POF) is affecting more and more women, which is the loss of function of the ovaries before age 40. To elucidate the underlying mechanisms of the oogenesis is of importance to understand the causes of impaired fertility and POF. However, mammalian oogenesis in vivo is a complex process. Thus, building an oogenesis visualizing system is beneficial for the study of oogenesis. In this study, we found that Figla is specifically expressed in female mice oocyte. Then, we constructed a lentiviral vector (pTRIP-Figla-EGFP-puro) under the control of Figla promoter, which drived enhanced green fluorescent protein (EGFP) as an indicator and used the lentiviral vector transduction the ovarian cells and induced germ cells derived from human umbilical cord mesenchymal stem cells (hUC-MSCs), and the results showed that the lentiviral vector we constructed was able to specifically express green fluorescent protein (GFP) in the ovarian oocyte and induced oocyte-like cells derived from hUC-MSCs, which was Figla-positive cells. These results suggest that pTRIP-Figla-EGFP vector provides a new system to study the role of Figla in oogenesis, and an approach to study the development and the differentiation of germ cells derived from stem cells.////////////////// | ||||
| Expression regulated by | mir212 | ||||
| Comment | MicroRNA-212 Post-Transcriptionally Regulates Oocyte-Specific Basic-Helix-Loop-Helix Transcription Factor, Factor in the Germline Alpha (FIGLA), during Bovine Early Embryogenesis. Tripurani SK 2013 et al. Factor in the germline alpha (FIGLA) is an oocyte-specific basic helix-loop-helix transcription factor essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. Here we report the characterization of bovine FIGLA gene and its regulation during early embryogenesis. Bovine FIGLA mRNA expression is restricted to gonads and is detected in fetal ovaries harvested as early as 90 days of gestation. FIGLA mRNA and protein are abundant in germinal vesicle and metaphase II stage oocytes, as well as in embryos from pronuclear to eight-cell stage but barely detectable at morula and blastocyst stages, suggesting that FIGLA might be a maternal effect gene. Recent studies in zebrafish and mice have highlighted the importance of non-coding small RNAs (microRNAs) as key regulatory molecules targeting maternal mRNAs for degradation during embryonic development. We hypothesized that FIGLA, as a maternal transcript, is regulated by microRNAs during early embryogenesis. Computational predictions identified a potential microRNA recognition element (MRE) for miR-212 in the 3' UTR of the bovine FIGLA mRNA. Bovine miR-212 is expressed in oocytes and tends to increase in four-cell and eight-cell stage embryos followed by a decline at morula and blastocyst stages. Transient transfection and reporter assays revealed that miR-212 represses the expression of FIGLA in a MRE dependent manner. In addition, ectopic expression of miR-212 mimic in bovine early embryos dramatically reduced the expression of FIGLA protein. Collectively, our results demonstrate that FIGLA is temporally regulated during bovine early embryogenesis and miR-212 is an important negative regulator of FIGLA during the maternal to zygotic transition in bovine embryos. ///////////////////////// | ||||
| Ovarian localization | Primordial Germ Cell, Oocyte | ||||
| Comment | Figla-Cre Transgenic Mice Expressing Myristoylated EGFP in Germ Cells Provide a Model for Investigating Perinatal Oocyte Dynamics. Lin RS 2014 et al. FIGLA (Factor in the germline, alpha) is a bHLH transcription factor expressed abundantly in female and less so in male germ cells. Mice lacking FIGLA do not form primordial follicles in the ovary and females are sterile, but there is no obvious phenotype in males. Using the Figla promoter to express Cre recombinase, we have established mEGFP/mTomato reporter mice with green germ cells and red somatic tissue. These mice were crossed into the Figla null background to accelerate perinatal oocyte loss. Live imaging of cultured newborn ovaries provides evidence that few oocytes egress and the vast majority disappear within the confines of the ovary. Although a cohort of mobile, phagocytic cells was observed, macrophage depletion in Csf1(op/op) mice did not affect oocyte loss. Investigations with TUNEL assays and caspase inhibitors suggest that apoptosis plays a role in the perinatal loss of oocyte in female mice. These results establish the utility of Figla-EGFP/Cre; mTomato/mEGFP in investigating germ cell dynamics in prepubertal mice. ///////////////////////// Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor. Joshi S et al. ABSTRACT: BACKGROUND: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, Alpha) and demonstrated its involvement in two independent developmental processes: formation of the primordial follicle and coordinate expression of zona pellucida genes. RESULTS: Taking advantage of Figla null mouse lines, we have used a combined approach of microarray and Serial Analysis of Gene Expression (SAGE) to identify potential downstream target genes. Using high stringent cutoffs, we find that FIGLA functions as a key regulatory molecule in coordinating expression of the NALP family of genes, genes of known oocyte-specific expression and a set of functionally un-annotated genes. FIGLA also inhibits expression of male germ cell specific genes that might otherwise disrupt normal oogenesis. CONCLUSIONS: These data implicate FIGLA as a central regulator of oocyte-specific genes that play roles in folliculogenesis, fertilization and early development. | ||||
| Follicle stages | Primordial, Primary, Secondary | ||||
| Comment | |||||
| Phenotypes |
POF (premature ovarian failure) |
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| Mutations |
4 mutations
Species: human
Species: mouse
Species: mouse
Species: None
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| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
| Links |
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| created: | Dec. 19, 2002, 8:25 p.m. | by: |
hsueh email:
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| last update: | Dec. 25, 2020, 8:44 p.m. | by: | hsueh email: |
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