KLUMPFUSS, A PUTATIVE DROSOPHILA ZINC-FINGER TRANSCRIPTION FACTOR, ACTS TO DIFFERENTIATE BETWEEN THE IDENTITIES OF 2 SECONDARY PRECURSOR CELLS WITHIN ONE NEUROBLAST LINEAGE

The similar to 300 distinct neurons comprising each hemineuromere of t he Drosophila embryonic central nervous system are derived from a segm entally reiterated array of similar to 30 progenitor sells, neuroblast s (NBs). Each NB has a unique identity and undergoes repeated cell div isions to product several smaller secondary precursor cells, ganglion mother cells (GMCs); each GMC divides once to produce two neurons and/ or glia, thereby generating a specific lineage of neurons/glia. Unders tanding the generation of neuronal diversity requires not only elucida tion of the molecules and mechanisms that specify NB identity but also those that act to differentiate between the cell types produced withi n one NB lineage. Here we show that the Drosophila Zn finger protein K lumpfuss (Klu), which shows sequence similarities to the mammalian Wil m's tumor suppressor (WT-1), acts to differentiate between the identit ies of the first two secondary precursor cells produced front one NB l ineage. Klu is expressed in the NB4-2 Lineage only after two rounds of NB cell division, in the second born GMC (GMC4-2b). In loss-of-functi on mutant embryos, the first born GMC (GMC4-2a) as well as its progeny neurons are duplicated; we show that this duplication of the GMC4-2a sublineage arises because GMC4-2b adopts the identity of GMC4-2a and d ivides to produce the GMC4-2a progeny. Moreover, when Klu is ectopical ly expressed in GMC4-2a, it fails to acquire its normal identity and f ails to produce correctly specified progeny. klu therefore acts to spe cify the identity of GMC4-2b and to make it distinct from GMC4-2a. Our findings further suggest that the determination of GMC cell fate occu rs in two steps; the initial GMC identity is the consequence of inheri tance from the maternal NB, however, the subsequent stabilization of t his identity requires functions like klu in the GMC.