Initiation of oogenesis and meiosis in the fetal ovary depends on Dennd1a-mediated production of Wnt5a and retinoic acid from the somatic niches.

The DENN (differentially expressed in neoplastic versus normal cells) domain containing 1A (Dennd1a), a guanine nucleotide exchange factor (GEF) for the small GTPase Rab35, is essential for mouse embryogenesis. Disruption of Dennd1a impairs the migration and differentiation of fetal germ cells. In the present study, we further elucidated the role of Dennd1a in oogenesis and meiosis in the fetal ovary. Ablation of Dennd1a disrupted the mRNA expression of Sohlh2, Figla, Stra8, and Rec8 in the ovary of Dennd1a-/- mutants at E13.5. Using ex vivo culture of E12.5 female gonads and adenoviral Dennd1a shRNA infection, we demonstrated that transcription of Sohlh2, Figla, Stra8 and Rec8 were not activated in the fetal ovary lacking Dennd1a. Dennd1a in the somatic cells might stimulate Sohlh2 expression at early stage of oocyte differentiation via regulating Wnt5a synthesis. On the other hand, meiotic initiation of the fetal germ cells required Dennd1a-mediated RA production from the somatic cells, which induced the expression of Stra8 and Rec8. Dennd1a could be involved in multiple signal pathways in the somatic cells that are critical for various processes of oogenesis and meiosis in the fetal ovary.