Gonadal Sex Differentiation: Supporting Versus Steroidogenic Cell Lineage Specification in Mammals and Birds

Abstract

The gonads of vertebrate embryos are unique among organs because they have a developmental choice; ovary or testis formation. Given the importance of proper gonad formation for sexual development and reproduction, considerable research has been conducted over the years to elucidate the genetic and cellular mechanisms of gonad formation and sexual differentiation. While the molecular trigger for gonadal sex differentiation into ovary of testis can vary among vertebrates, from egg temperature to sex-chromosome linked master genes, the downstream molecular pathways are largely conserved. The cell biology of gonadal formation and differentiation has long thought to also be conserved. However, recent discoveries point to divergent mechanisms of gonad formation, at least among birds and mammals. In this mini-review, we provide an overview of cell lineage allocation during gonadal sex differentiation in the mouse model, focusing on the key supporting and steroidogenic cells and drawing on recent insights provided by single cell RNA-sequencing. We compare this data with emerging information in the chicken model. We highlight surprising differences in cell lineage specification between species and identify gaps in our current understanding of the cell biology underlying gonadogenesis.

Single-cell transcriptomic profiling redefines the origin and specification of early adrenogonadal progenitors

“…We used our single-cell dataset comprising cells from all three layers of mesodermal derivatives (paraxial, lateral and intermediate) present at E9.0 in the posterior trunk to show that in mouse, early AGP cells are ontogenically related to the splanchnic lateral plate mesoderm. The relevance of different origins for the AGP among vertebrates-LPM in mouse (this study) and IM in chicken (Estermann et al, 2020a; Sekido and Lovell-Badge, 2007; Yoshioka et al, 2005)-is not clear, but it has been proposed to be linked to differences in mesonephros excretory function and/or evolution of master sex-determining switches genes (Estermann et al, 2020b). Interestingly, we observed discrepancies between Nr5a1 - eGFP transgene and endogenous Nr5a1 expression, with GFP being expressed in a subset of Pax2 + / Nr5a1 - intermediate mesoderm at E9.0 (data not shown).…”

Teaching About Sex and Gender in Neuroscience: More than meets the "XY"

“…Figures 1-3 in McCarthy (2020) may serve as a replacement or, at least, a complement to the traditional gross anatomy differentiation chart. Additionally, see Figure 1 in Estermann et al (2020) for a visual rendering of the cellular architecture resulting from gonadal sex differentiation as well as Figures 1 and 2 in Grinspon and Rey (2019).…”

Ovary Development: Insights From a Three-Dimensional Imaging Revolution

“…These support cells eventually form what has been considered a supportive niche for the oocyte. The earliest gonad precursor cells originate from a thickening of the mesenchyme on the ventromedial side of the embryonic kidney (mesonephros), to which a cohort of coelomic epithelial cells migrate and proliferate; these two precursors establish the supporting steroidogenic and interstitial cells of the genital ridges [reviewed in Estermann et al (2020) ]. ‘Pre-granulosa’ cell populations emerge at different stages of ovarian development and contribute to the formation of distinct pools of follicles.…”