ONLY A SUBSET OF THE BINARY CELL FATE DECISIONS MEDIATED BY NUMB NOTCH SIGNALING IN DROSOPHILA SENSORY ORGAN LINEAGE REQUIRES SUPPRESSOR OFHAIRLESS/

In Drosophila, an adult external sensory organ (bristle) consists of f our distinct cells which arise from a sensory organ precursor cell via two rounds of asymmetric divisions, The sensory organ precursor cell first divides to generate two secondary precursor cells, IIa and IIb T he IIa cell then divides to produce the hair cell and the socket cell, Shortly after, the IIb cell divides to generate the neuron and the sh eath cell, The membrane-associated protein Numb has been shown to be r equired for the first two asymmetric divisions, We now report that a n ew hypomorphic numb mutant not only displays a double-socket phenotype , due to a hair cell to socket cell transformation, but also a double- sheath phenotype? due to a neuron to sheath cell transformation, This provides direct evidence that numb functions in the neuron/sheath cell lineage as well, Those results, together with our observation from im munofluorescence analysis that Numb forms a crescent in the dividing I Ia and IIb cells suggest that asymmetric localization of Numb is impor tant for the cell fate determination in all three asymmetric cell divi sions in the sensory organ lineage, Interestingly, we found that in th e hair/socket cell lineage but not the neuron/sheath cell lineage, a S uppressor of Hairless mutation acts as a dominant suppressor of numb m utations whereas Hairless mutations act as enhancers of numb. Moreover , epistasis analysis indicates that Suppressor of Hairless acts downst ream of numb, and results from in vitro binding analysis suggest that the genetic interaction between numb and Hair less may occur through d irect protein-protein interaction, These studies reveal that Suppresso r of Hairless is required for only a subset of the asymmetric division s that depend on the function of numb and Notch.