genomic atlas of human adrenal and gonad development

In humans, the adrenal glands and gonads undergo distinct Background biological events between 6-10 weeks post conception (wpc), such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. : RNA was extracted from 53 tissue samples between 6-10 wpc Methods (adrenal, testis, ovary and control). Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. : Using this approach, we have identified novel components of adrenal Results development (e.g. , ) and confirmed the role of as the main ASB4 NPR3 SRY human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with in the testis (e.g. ), SOX9 CITED1 which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. , , , , ), as well as testis MGARP FOXO4 MAP3K15 GRAMD1B RMND2 biomarkers (e.g. ). We have also shown that the developing human SCUBE1 ovary expresses distinct subsets of genes (e.g. , ), but OR10G9 OR4D5 enrichment for established biological pathways is limited. : This genomic atlas is revealing important novel aspects of human Conclusion development and new candidate genes for adrenal and reproductive disorders. 1 1 1 1