Mechano-regulation of germline development, maintenance, and differentiation

Abstract

Biochemical signaling arising from mechanical force-induced physical changes in biological macromolecules is a critical determinant of key physiological processes across all biological lengths and time scales. Recent studies have deepened our understanding of how mechano-transduction regulates somatic tissues such as those in alveolar, gastrointestinal, embryonic, and skeleto-muscular systems. The germline of an organism has a heterogeneous composition - of germ cells at different stages of maturation and mature gametes, often supported and influenced by their accessory somatic tissues. While biochemical signaling underlying germline functioning has been extensively investigated, a deeper interest in their mechanical regulation has been gaining traction in recent years. In this review, we delve into the myriad ways in which germ cell development, maintenance, and functions are regulated by mechanical forces.

Keywords: Cell adhesion; Cell fate; Cytoskeleton; Germline; Mechanics; Mechano-transduction.

Fig. 1

Drosophila egg chamber development is associated with changes in cell number, cell shape and an overall structural morphogenesis. (A) The follicles at different stages of maturation from the initial germarium to the oocyte at the end. (B) The germarium with developing follicles at different stages and characteristic shapes. (C) A matured follicle with the nurse cells, oocyte and the surrounding follicle cells. The nurse cells and oocyte are connected by cytoplasmic bridges called ring canals (inset) formed of an outer rim of plasma membrane (black) and inner rim of actin-myosin network (red).

Fig. 2

Mammalian Germline. (A) The mammalian ovary with follicles at different stages of development and degeneration arranged on a common stroma. (B) The matured oocyte is surrounded by a few layers of granulosa cells, that act as nurse cells. These cells are in constant contact with the oocyte by cytoplasmic extensions called Transzonal projections (TZP). (C) In the mammalian testis, seminiferous tubules are lined with larger sertoli cells (pink) and spermatozoa at different stages of maturation (blue) attached to the Sertoli cells. (D) Specialised cell-cell contacts are found in the interfaces of germ-germ cell or germ-sertoli cell junctions.

Fig. 3

A schematic showing germ cells in the adult Caenorhabditis elegans hermaphrodite gonad. (A) The gonad consists of two U-shaped arms flanking a common uterus. Each arm consists of a somatic DTC and sheath cells that envelope the germ cells. This structure is encased by a basement membrane. (B) DTC, at the distal edge of the gonad migration, maintains the germline stem cells. (C & D) The syncytial gonad at various stages of meiotic development surrounds a common rachis with a cytoplasmic flow from distal to proximal end (red arrows). Germline cells that undergo physiological apoptosis support oogenesis by contributing their cellular contents to the growing oocytes. (E) The Spermatheca houses a number of matured spermatozoa. Fertilisation takes place upon entry of a matured oocyte from the distal side and its exit into the uterus post-fertilisation. This process is supported by the opening and closing of the spermathecal valves.

Fig. 4

Cytoplasmic streaming. (A) A matured Drosophila follicle showing microtubule arrangement and cytoplasmic streaming in the oocyte. (B) A Meiotic II stage mice oocyte showing the actomyosin cortex, asymmetrically placed spindle assembly and cytoplasmic streaming direction.

Fig. 5

Mechano-regulation of the Germline has similar mechanisms across organisms. The mechanical stimuli arise from either extrinsic (pink) or intrinsic sources (yellow). These stimuli are transduced by mechanotransducers shown along the inner green ring. Feedback reinforcement of these mechanical stimuli brings about modified cellular behaviour as depicted in the blue outer circle.