Parietal endoderm (PE) migration is the first long-range migratory event in the mammalian embryo contributing to the parietal yolk sac. PE migration can be studied in vitro using the F9 teratocarcinoma stem cell model system. We have found that PE migration is directed and modulated via the Planar Cell Polarity (PCP) pathway through Rho/ROCK signaling. Wnt inhibition using sFRP results in a loss of orientation, visualized by Golgi apparatus localization, along with disorganized microtubules and a lack of robust focal adhesions. Small GTPases are downstream of PCP signaling and Rho/ROCK inhibition results in a loss of orientation, whereas inhibition of Rac does not affect PCP. Activation of canonical Wnt signaling combined with Wnt inhibition does not prevent loss of oriented migration. These data support a role for non-canonical Wnt/PCP signaling directing oriented migration of PE.
