The embryonic ontogeny of the gonadal somatic cells in mice and monkeys

Abstract

Highlights d Ontogeny of the gonads in mice and monkeys defined by single-cell transcriptomics d Temporally distinct contribution of T + descendants to the gonads and related organs d The gonads originate from the T + primitive streak through posterior intermediate mesoderm d The gonads acquire an epithelial-mesenchymal hybrid state upon specification

The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys

“…S1D). These findings are consistent with previous studies on mice and cynomolgus monkey embryos and suggest that CE originates from posterior intermediate mesoderm (8).…”

“…S2, A and B). These findings reveal that human gonadogenesis is initiated at CS14 to CS15 through the sequential activation of GATA4 and NR5A1 within the posterior CE, similar to mice and cynomolgus monkeys (8,15).…”

“…Specifically, through histologic and transcriptomic analyses of early human gonadogenesis, we found that the gonad is established from the posterior CE at 4 to 5 wpf through the sequential activation of GATA4 (4 wpf, CS14) and NR5A1 (5 wpf, CS15), similar to mice and cynomolgus monkeys (Fig. 5 8). A previous single-cell RNA sequencing (scRNA-seq) study suggested that NR5A1 is not activated in the early gonad and GATA4 only appears at 6 to 7 wpf when testicular cord formation is initiated (21).…”

“…We previously demonstrated that in both mice and cynomolgus monkeys, the posterior intermediate mesoderm gives rise to KRT19 + CE, which, in turn, sequentially expresses GATA4 and NR5A1 to acquire the gonadal fate at E10 (embryonic day 10) in mice and E31 in cynomolgus monkeys ( 8 ). To precisely determine the specification timing of human gonads, we analyzed serial paraffin sections of human embryos at various stages (CS12, n = 1; CS13, n = 3; CS14, n = 1; CS15, n = 3; CS16, n = 2; CS17, n = 1; table S1).…”

“…Mammalian gonads (ovaries and testes) also produce steroid hormones and commonalities exist between the adrenal cortex and gonads in both their steroid synthetic pathways and developmental origin. Lineage tracing studies in mice reveal that the adrenal cortex and gonads originate from a common progenitor, the adrenogonadal primordium (4)(5)(6)(7)(8)(9). The adrenogonadal primordium expresses GATA4 and WT1, along with NR5A1, and is thought to be established through thickening of coelomic epithelium (CE), which is a derivative of the posterior intermediate mesoderm (6)(7)(8).…”