THE DIFFERENTIATION OF THE SEROTONERGIC NEURONS IN THE DROSOPHILA VENTRAL NERVE CORD DEPENDS ON THE COMBINED FUNCTION OF THE ZINC-FINGER PROTEINS EAGLE AND HUCKEBEIN

The Drosophila ventral nerve cord (vNC) derives from a stereotyped pop ulation of neural stem cells, neuroblasts (NBs), each of which gives r ise to a characteristic cell lineage. The mechanisms leading to the sp ecification and differentiation of these lineages are largely unknown. Here we analyse mechanisms leading to cell differentiation within the NB 7-3 lineage, Analogous to the grasshopper, NB 7-3 is the progenito r of the Drosophila vNC serotonergic neurons. The zinc finger protein Eagle (Eg) is expressed in NB 7-3 just after delamination and is prese nt in all NB 7-3 progeny until late stage 17. DiI cell lineage tracing and immunocytochemistry reveal that eg is required for normal pathfin ding of interneuronal projections and for restricting the cell number in the thoracic NB 7-3 lineage. Moreover, eg is required for serotonin expression. Ectopic expression of Eg protein forces specific addition al CNS cells to enter the serotonergic differentiation pathway. Like N B 7-3, the progenitor(s) of these ectopic cells express Huckebein (Hkb ), another zinc finger protein. However, their progenitors do not expr ess engrailed (en) as opposed to the NB 7-3 lineage, where en acts ups tream of eg. We conclude that eg and hkb act in concert to determine s erotonergic cell fate, while en is more distantly involved in this pro cess by activating eg expression. Thus, we provide the first functiona l evidence for a combinatorial code of transcription factors acting ea rly but downstream of segment polarity genes to specify a unique neuro nal cell fate.