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

Jiang Fu,Jingjing Shi,Jinlong Ma,Qing Gao,Qun Niu

doi:10.52586/5045

Abstract

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.

Highlights

The DENN domain containing 1A (Dennd1a) functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rab35
At E11.5 during mouse embryo development, Dennd1a protein was found in both the hindgut mesentery and genital ridge of mouse embryos (Fig. 1A), suggesting Dennd1a may play a role when primordial germ cells (PGCs) are migrating through the mesentery and colonized in the genital ridge
The results suggest that Akt/βcatenin pathways may be involved in Dennd1a-mediated Wnt5a and Retinoic acid (RA) production in the somatic cells during fetal germ cell development

Summary

Introduction

The DENN (differentially expressed in neoplastic versus normal cells) domain containing 1A (Dennd1a) functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rab. The DENN (differentially expressed in neoplastic versus normal cells) domain containing 1A (Dennd1a) functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rab35 It mediates the switch from GDP-bound Rab to GTP-bound form, to promote endocytic recycling of various cargoes on clathrin-coated vesicles (CCVs) after internalization [1,2,3]. Disruption of Dennd1a impairs the migration and differentiation of fetal germ cells [7]. Dennd1a deficiency affects the migration of PGCs and results in a significant reduction in gonadal germ cell numbers [7]

Methods

Results

Discussion

Conclusion