Investigating epithelial progenitors commitment during gonadal development

Sex determination is the process by which the bipotential gonad develops into either a testis or an ovary, depending on the genetic sex of the embryo. The bipotential gonad comprises two major somatic lineages derived from multipotent coelomic epithelium (CE) progenitors: the supporting and steroidogenic lineages. Upstream of sex determination lies an equally fundamental biological process: multipotent progenitors of the coelomic epithelium diversify and restrict their fate toward either the supporting or steroidogenic lineage.

Preliminary results showed that CE progenitors of fetal mouse ovary are transcriptionally heterogeneous and spatially pre-patterned into fate-biased subpopulations before ingression into the gonadal mesenchyme. The CE undergoes a temporally regulated sequence of fate priming, initially biased toward steroidogenic fate, followed by a transient coexistence of supporting and steroidogenic -biased progenitors, and ultimately restricted to a supporting-identity.

In my thesis project, I aim to better understand if CE progenitors covering the developing gonad comprise transcriptionally distinct and spatially organized subpopulations already biased toward specific fates or whether lineage specification occurs only after delamination. In addition, this project will investigate the temporal dynamics, spatial organization, and underlying mechanisms governing the specification of CE progenitors as well as the conservation of those mechanisms between the male and female gonad.

To address this central question, I will be using a combination of single-cell RNA sequencing (scRNAseq) of mouse gonadal development as well as high-resolution spatial transcriptomics and in vivo validations to investigate the earliest steps of somatic fate allocation in the

developing gonad.

By identifying the early mechanisms that bias somatic cell fate in the gonad, this project will provide a developmental framework to better understand the cellular origins of differences of sex development and gonadal dysgenesis.