SUMMARYDuring development, specific cells are eliminated by apoptosis to ensure that the correct number of cells is integrated in a given tissue or structure. How the apoptosis machinery is activated selectively in vivo in the context of a developing tissue is still poorly understood. In the Drosophila ovary, specialised follicle cells [polar cells (PCs)] are produced in excess during early oogenesis and reduced by apoptosis to exactly two cells per follicle extremity. PCs act as an organising centre during follicle maturation as they are the only source of the JAK/STAT pathway ligand Unpaired (Upd), the morphogen activity of which instructs distinct follicle cell fates. Here we show that reduction of Upd levels leads to prolonged survival of supernumerary PCs, downregulation of the pro-apoptotic factor Hid, upregulation of the anti-apoptotic factor Diap1 and inhibition of caspase activity. Upd-mediated activation of the JAK/STAT pathway occurs in PCs themselves, as well as in adjacent terminal follicle and interfollicular stalk cells, and inhibition of JAK/STAT signalling in any one of these cell populations protects PCs from apoptosis. Thus, a Stat-dependent unidentified relay signal is necessary for inducing supernumerary PC death. Finally, blocking apoptosis of PCs leads to specification of excess adjacent border cells via excessive Upd signalling. Our results therefore show that Upd and JAK/STAT signalling induce apoptosis of supernumerary PCs to control the size of the PC organising centre and thereby produce appropriate levels of Upd. This is the first example linking this highly conserved signalling pathway with developmental apoptosis in Drosophila.

The linotte (lio) mutant was first isolated as a memory mutant. The lio gene encodes a putative receptor tyrosine kinase (RTK), homologous to the human protein RYK. This gene has been independently identified in a screen for embryonic nervous system axonal guidance defects and called derailed (drl). Here, we report that linotte mutants present structural brain defects in the adult central complex (CX) and mushroom bodies (MB). linotte and derailed are allelic for this phenotype, which can be rescued by a drl+ transgene. The Lio RTK is expressed preferentially in the adult CX and MB. Our results suggest that, analogous to its role within the embryonic nervous system, the Lio RTK is involved in neuronal pathway selection during adult brain development.