Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells.

The four cells of an external sense organ in the Drosophila peripheral nervous system, the neuron, its sheath cell, and two "outer support cells" that form the hair and socket, are derived from a common precursor, the sensory organ precursor (SOP), after two rounds of division. We determined by immunocytochemistry that numb is a membrane-associated protein which localizes asymmetrically to one-half of the predivisional SOP cell. Upon division, numb segregates differentially to one daughter. Loss of numb function causes the descendants of the SOP to differentiate inappropriately, producing four outer support cells and no neuron or sheath. Ectopic expression of numb during the time of SOP division results in a transformation that is opposite to the null mutant transformation. Thus, numb functions to determine the fates of the secondary precursors; the differential distribution of numb as the SOP divides generates an asymmetric division in which the daughter cells acquire distinct identities.