CDC42 shapes up the epicardium Free

The epicardium – a single layer of cells that covers the heart – contributes to multiple cardiac lineages and is essential for heart development and regeneration. During development, the epicardium arises from a transient structure known as the pro-epicardium (PE): pro-epicardial cells (PECs) dissociate from the PE, translocate across the pericardial cavity and attach to the heart surface. The molecular and cellular mechanisms that control this process have thus far been elusive but, now, Mingfu Wu and co-workers reveal four different mechanisms of PEC translocation to myocardium and a key role for the small GTPase CDC42 during epicardial development in mice (p. 1635). They first report that the conditional knockout of Cdc42 in PECs results in epicardial defects, with PECs failing to form villous protrusions and floating cysts and failing to translocate to the myocardium. The authors further demonstrate that Cdc42 null PECs exhibit loss of polarity and impaired cell dynamics. Finally, they reveal that CDC42 also regulates the trafficking of FGFR1 in PECs and hence is likely to be required for FGF2-mediated signalling activity in these cells. Overall, these findings provide new insights into the mechanism by which the epicardium forms and highlight a pivotal role for CDC42 in epicardial development.