split ends encodes large nuclear proteins that regulate neuronal cell fateand axon extension in the Drosophila embryo

split ends (spen) encodes nuclear 600 kDa proteins that contain RNA recogni tion motifs and a conserved C-terminal sequence. These features define a ne w protein family, Spen, which includes the vertebrate MINT transcriptional regulator, Zygotic spen mutants affect the growth and guidance of a subset of axons in the Drosophila embryo. Removing maternal and zygotic protein el icits cell-fate and more general axon-guidance defects that are not seen in zygotic mutants. The wrong number of chordotonal neurons and midline cells are generated, and we identify defects in precursor formation and EGF rece ptor-dependent inductive processes required for cell-fate specification. Th e number of neuronal precursors is variable in embryos that lack Spen, The levels of Suppressor of Hairless, a key transcriptional effector of Notch r equired for precursor formation, are reduced, as are the nuclear levels of Yan, a transcriptional repressor that regulates cell fate and proliferation downstream of the EGF receptor. We propose that Spen proteins regulate the expression of key effecters of signaling pathways required to specify neur onal cell fate and morphology.