split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo.
split ends (spen) encodes nuclear 600 kDa proteins that contain RNA recognition motifs and a conserved C-terminal sequence. These features define a new 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 elicits 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 receptor-dependent inductive processes required for cell-fate specification. The number of neuronal precursors is variable in embryos that lack Spen. The levels of Suppressor of Hairless, a key transcriptional effector of Notch required 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 effectors of signaling pathways required to specify neuronal cell fate and morphology.
Kuang
B
B
Howard Hughes Medical Institute, Department of Cell Biology, Vanderbilt University Medical Center, Nashville TN 37232-0295, USA.
Wu
S C
SC
Shin
Y
Y
Luo
L
L
Kolodziej
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C402387:Spen protein, Drosophila