Joshi Saurabh, Davies Holly, Sims Lauren Porter, Levy Shawn E, Dean Jurrien
Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
BMC Dev Biol. 2007 Jun 13;7:67. doi: 10.1186/1471-213X-7-67.
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.
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.
These data implicate FIGLA as a central regulator of oocyte-specific genes that play roles in folliculogenesis, fertilization and early development.
哺乳动物的卵巢卵泡发生是一个复杂的过程,涉及生殖细胞与体细胞之间的相互作用。成功需要精心编排转录因子、细胞粘附分子和生长因子的表达。我们鉴定出一种生殖细胞特异性的碱性螺旋-环-螺旋转录因子FIGLA(生殖系α因子),并证明其参与两个独立的发育过程:原始卵泡的形成和透明带基因的协调表达。
利用Figla基因敲除小鼠品系,我们采用微阵列和基因表达序列分析(SAGE)相结合的方法来鉴定潜在的下游靶基因。使用高严格阈值,我们发现FIGLA作为关键调节分子,协调NALP基因家族、已知卵母细胞特异性表达基因以及一组功能未注释基因的表达。FIGLA还抑制雄性生殖细胞特异性基因的表达,否则这些基因可能会破坏正常的卵子发生。
这些数据表明FIGLA是卵母细胞特异性基因的核心调节因子,这些基因在卵泡发生、受精和早期发育中发挥作用。