To function correctly, the epithelial cells that line the tubes and air sacs of mammalian lungs need to be polarised. Little is known about the mechanisms that control cell polarity in the lung epithelium but now, on p. , David Warburton and co-workers implicate the protein phosphatase Eya1 in cell polarity control in the mouse distal embryonic lung epithelium, which represents the epithelial progenitor pool. The researchers show that distal embryonic lung epithelium is polarised with characteristic perpendicular cell divisions. They report that several spindle orientation-regulatory proteins and the cell fate determinant Numb are asymmetrically localised in distal embryonic lung epithelium. Furthermore, interfering with the function of these proteins in vitro randomises spindle orientation and alters cell fate. Importantly, the researchers show that interfering with Eya1 function in vivo or in vitro results in defective epithelial cell polarity and mitotic spindle orientation, disrupts Numb segregation, and inactivates Notch signalling, thereby establishing Eya1 as a crucial regulator of the complex behaviour of distal embryonic lung epithelium.
