Numb regulates somatic cell lineage commitment during early gonadogenesis in mice

Abstract

During early gonadogenesis, proliferating cells in the coelomic epithelium (CE) give rise to most somatic cells in both XX and XY gonads. Previous dye-labeling experiments showed that a single CE cell could give rise to additional CE cells and to both supporting and interstitial cell lineages, implying that cells in the CE domain are multipotent progenitors, and suggesting that an asymmetric division is involved in the acquisition of gonadal cell fates. We found that NUMB is asymmetrically localized in CE cells, suggesting that it might be involved. To test this hypothesis, we conditionally deleted Numb on a Numb-like mutant background just prior to gonadogenesis. Mutant gonads showed a loss of cell polarity in the surface epithelial layers, large interior cell patches expressing the undifferentiated marker LHX9, and loss of differentiated cells in somatic cell lineages. These results indicate that NUMB is necessary for establishing polarity in CE cells, and that asymmetric divisions resulting from CE polarity are required for commitment to differentiated somatic cell fates. Surprisingly, germ cells, which do not arise from the CE, were also affected in mutants, which may be a direct or indirect effect of loss of Numb.