Proliferation of germ cells during gonadal sex differentiation in medaka: Insights from germ cell-depleted mutant zenzai

Abstract

The proliferation of germ cells becomes sexually dimorphic during gonadal sex differentiation, although the underlying dynamics of this are not well understood in vertebrates. By tracing GFP-labeled germ cells in vivo and analyzing the germ cell-depleted mutant, zenzai, we show that the proliferation and differentiation of germ cells are regulated in a sexually dimorphic manner in the teleost fish medaka. In the undifferentiated gonads, germ cells resume proliferation by slow intermittent division (type I), producing isolated daughter cells. While germ cells in the male gonads continue this mode of proliferation, some germ cell fractions in the female gonads initiate two to four rounds of continuous division (type II), forming cysts of four, eight, or sixteen cells, which subsequently enter meiosis synchronously. Thus, female germ cells become differentiated much earlier than do male germ cells. In the zenzai mutant, a defect in slow intermittent division eventually leads to the depletion of germ cells in the adult gonads in both sexes, despite the fact that cyst-forming division is unaffected. This argues that slow intermittent division is essential for the maintenance of germ cells. The proliferation and differentiation of germ cells are thus important components of gonadal sex differentiation in vertebrates.

Germline Cysts and the Formation of the Germinal Epithelium During the Female Gonadal Morphogenesis in Cyprinus carpio (Teleostei: Ostariophysi: Cypriniformes)

“…In a similar fashion to C. carpio, Saito et al (2007) reported the sexual discernment as an early event during gonad development in Oryzias latipes that was signaled by one of two types of germ cell proliferation. Type I proliferation involved the stem cell self-renewal and produced isolated daughter cells.…”

“…In a fashion that is similar to that which occurs in the ovarian germinal epithelium lining the ovigerous lamellae in sexually mature females (Grier, 2000;Le Menn et al, 2007;Grier et al, 2009), and also in the differentiating ovary of Oryzias latipes (Saito et al, 2007) and C. carpio, individual oogonia divide mitotically forming a germline cyst of interconnected germ cells that synchronously enter into meiosis, becoming oocytes. ''Cysts are groups of cells that form from a single founder cell.…”

“…They are composed of intimately associated groups of germ cells that are interconnected by distinctive intercellular bridges that form as a result of incomplete cytokinesis (see reviews by Spradling, 1993;Pepling et al, 1999;Matova and Cooley, 2001;Pepling, 2006). During ovarian differentiation in the beloniform, Oryzias latipes, cyst-forming divisions of oogonia, were recently shown in an elegant report by Saito et al (2007). However, in ovaries of adult fish, the sites of germ cell proliferation in the germinal epithelium that borders the ovigerous lamellae are known as nests (Selman et al, 1993).…”

“…In general, they focus on the origin of the primordial germ cells and the interaction of these with the somatic cells in the early developing gonads. These descriptions, excepting that by Saito et al (2007), are based primarily on histological cross sections during early gonadal development and provide a localized view of the process. Many of them present ultrastructural information.…”

Germline stem cells are critical for sexual fate decision of germ cells

“…The interconnected germ cells are packaged as a cyst and surrounded by somatic cells. Following several rounds of mitosis, the cells enter meiosis to become eggs in the ovary or sperms in the testis 28, 29. Interestingly, the number of successive division rounds differs between oogenesis and spermatogenesis in medaka 20, 30.…”