Early gonadogenesis in mammals: Significance of long and narrow gonadal structure

Abstract

In mammalian embryogenesis, the gonadal primordium arises from the thickening of the coelomic epithelium, which results in a pair of extremely long and narrow gonadal structures along the anteroposterior axis. These gonadal structures are conserved in various mammalian species, suggesting a great advantage in properly receiving migrating primordial germ cells (PGCs) that are widely scattered throughout the hindgut tube. Soon after the PGCs settle, the bipotential gonads undergo sex determination into testes or ovaries by the sex-determining gene, Sry, which is expressed in supporting cell precursors in a center-topole manner. Such a long, narrow gonadal structure bestows a considerable time lag on Sry expression between the center and pole regions, but testiculogenesis with cord formation and Leydig cell differentiation occurs synchronously throughout the whole organ. This synchronous testiculogenesis could be explained by a positive-feedback mechanism between SOX9 (another SRY-related transcription factor) and FGF9 downstream of Sry. FGF signals are likely secreted from the center region, rapidly diffuse into the poles, and then induce the establishment of SOX9 expression in Sertoli cells in the pole domains. This work focuses on recent knowledge of the molecular and cellular events of PGC migration, gonadogenesis, and testiculogenesis, and their biological significance in mammalian embryogenesis. Developmental Dynamics 242:330-338,

Building the mammalian testis: origins, differentiation, and assembly of the component cell populations

“…Around 10 dpc, the germ cells finally come to occupy the genital ridges by migrating anteriorly through the hindgut mesentery. It has been speculated that the long and narrow structure of the genital ridges is important for capturing the migrating germ cells that are widely scattered along the hindgut (Harikae et al 2013). At this point, the germ cells lose their motility and polarized morphology (Baillie 1964;Donovan et al 1986) and are referred to as gonocytes.…”

“…When genital ridges are cut into three segments and cultured, testis cords do not form in the polar segments unless exogenous FGF9 is supplied, implicating rapid poleward diffusion of FGF9 in stimulating cord formation (Hiramatsu et al 2010). Such a mechanism has been proposed to explain why cord formation occurs synchronously throughout the testis despite the wave of Sry and Sox9 expression that moves outward from the center of the genital ridge (Harikae et al 2013).…”

A novel Amh-Treck transgenic mouse line allows toxin-dependent loss of supporting cells in gonads

“…As the first morphological sign of testis differentiation, germ cells are surrounded by differentiating Sertoli cells, leading to the formation of testis cords (future seminiferous tubules), a tubular structure of the germ and Sertoli cells packed within the basal lamina sheath (Harikae et al 2013a, Svingen & Koopman 2013. In developing ovaries, both germ and pre-granulosa cells also aggregate to form the poorly defined ovarian cords (ovigerous cord), subsequently resulting in the formation of ovarian cysts, a closed sack-like structure of several oocytes and their surrounding pre-granulosa cells (Pepling 2006, Hummitzsch et al 2013.…”

Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries

“…In XY males, Sry is transiently [11.0-12.0 days post coitum (d.p.c.)] activated in a center-to-pole wave-like pattern along the anteroposterior (AP) axis of the indifferent XY gonads (Harikae et al, 2013). In these bipotential supporting cells, SRY directly upregulates another, autosomal Sry-box gene, Sox9 (Sekido and Lovell-Badge, 2008), and Sox9 induces Fgf9 expression in a similar center-to-pole pattern (Kim et al, 2006;Hiramatsu et al, 2010).…”