RNA-binding proteins in human oogenesis: Balancing differentiation and self-renewal in the female fetal germline

Abstract

Primordial germ cells undergo three significant processes on their path to becoming primary oocytes: the initiation of meiosis, the formation and breakdown of germ cell nests, and the assembly of single oocytes into primordial follicles. However at the onset of meiosis, the germ cell becomes transcriptionally silenced. Consequently translational control of pre-stored mRNAs plays a central role in coordinating gene expression throughout the remainder of oogenesis; RNA binding proteins are key to this regulation. In this review we examine the role of exemplars of such proteins, namely LIN28, DAZL, BOLL and FMRP, and highlight how their roles during germ cell development are critical to oogenesis and the establishment of the primordial follicle pool.

Keywords: BOLL; DAZL; FMRP; Germ cell differentiation; LIN28; RNA binding proteins.

Fig. 1

LIN28, DAZL, BOLL and FMRP expression during germ cell differentiation in females. Cartoon schematic depicts spatial and temporal organisation of germ cells within the human fetal ovary. Germ cells at different stages of maturation are represented by progressively darker shades of orange. LIN28 is present in PGCs. DAZL is expressed before the onset of meiosis but down-regulated afterwards; BOLL is transiently expressed at later stages of meiosis with minimal overlap with DAZL. DAZL is re-expressed in oocytes within primordial follicles. FMRP is present in pre-meiotic germ cells, and yellow dots represent granulation of FMRP staining at the onset of meiosis (Section 2.4).

Fig. 2

LIN28, DAZL and BOLL expression in human fetal ovary. Tiled image of 15wga human fetal ovary section depicts LIN28 positive germ cells (red) in the periphery of the ovary (arrowheads), whilst DAZL positive germ cells (green) are more mature and located further from the ovary edge (arrows). BOLL positive germ cells (blue) are more centrally located and have a larger diameter size (asterisks). There is no co-localisation between LIN28, DAZL or BOLL (as observed in merge image).

Fig. 3

FMRP co-expression with various markers of germ cell development and RNA granules. There is limited overlap between FMRP and LIN28. Expression of the meiosis marker SYCP3 correlates with FMRP granulation (white arrowheads) in most but all of germ cells, suggesting that FMRP granulation precedes SYCP3 expression. There is a degree of association between FMRP and RNA granule markers GW182 and G3BP, respectively.