Cell News-How Primary Cilia Find Their Place in Skin

The skin game—the first step to making epidermal tissue is the correct localization of basal bodies that anchor primary ciliary. Flickr Commons hoto by cheriejoyful

Primary cilia have been the glamour organelles of the early 21^st century. First implicated in polycystic kidney disease in 2000, primary cilia now play so many roles in so many defects and diseases that the term, ciliopathies, was coined to encompass them. Clearly primary cilia also have a part in healthy cell and tissue differentiation especially during embryogenesis but exactly how they work in the development of tissue such as the epidermis has been poorly understood.

Now ASCB members Ellen Ezratty and Elaine Fuchs plus colleague H. Amalia Pasolli at the Rockefeller University have traced a pathway where primary cilia respond to Notch signaling to localize at cell-cell borders in the first few basal layers of the developing epidermis. Critical to the process is the Presenilin-2 protein, which arrives via a targeting motif called VxPx. But when the motif is mutated, Presenilin-2 still turns up but the proper location of basal bodies that anchor primary cilia is lost. The missing piece, say the researchers, is the small GTPase ARF4. Without ARF4, Presenilin-2 doesn’t localize the basal bodies correctly, Notch signaling goes awry, and epidermal differentiation goes wrong. This, say the researchers, makes ARF4 more than a bystander in epidermal differentiation but instead a driver of Notch signaling that gets primary cilia into position. Their paper appears in the Journal of Cell Biology.