Analysis of the niche for mouse germ cell specification

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In the mouse, the formation of primordial germ cells (PGCs) is influenced by BMP4 and WNT3 activity. Embryos lacking Dullard activity fail to form PGCs. We found mutations in Dullard had no detectable effect on BMP4. Results of the genetic study showed that loss of Dullard has no discernible effect on the expression of Bmp4 and Smads, and does not affect the dose-dependent inductive activity of BMP4 on PGC formation. Instead, Dullard functions as an agonist that modulates WNT signalling activity to facilitate the formation of PGC precursors. Loss of Dullard function was accompanied by down-regulation of WNT/beta-catenin signalling activity and a reduction in the level of Dishevelled 2 (Dvl2). Therefore, Dullard may play a role in the fine-tuning of WNT signaling activity, which is crucial for the specification of the germ cell lineage.