A positive role for Patched in Hedgehog signaling revealed by the intracellular trafficking of Sex-lethal, the Drosophila sex determination master switch.
The sex determination master switch, Sex-lethal (Sxl), controls sexual development as a splicing and translational regulator. Hedgehog (Hh) is a secreted protein that specifies cell fate during development. We show that Sxl is in a complex that contains all of the known Hh cytoplasmic components, including Cubitus interruptus (Ci) the only known target of Hh signaling. Hh promotes the entry of Sxl into the nucleus in the wing disc. In the anterior compartment, the Hh receptor Patched (Ptc) is required for this effect, revealing Ptc as a positive effector of Hh. Some of the downstream components of the Hh signaling pathway also alter the rate of Sxl nuclear entry. Mutations in Suppressor of Fused or Fused with altered ability to anchor Ci are also impaired in anchoring Sxl in the cytoplasm. The levels, and consequently, the ability of Sxl to translationally repress downstream targets in the sex determination pathway, can also be adversely affected by mutations in Hh signaling genes. Conversely, overexpression of Sxl in the domain that Hh patterns negatively affects wing patterning. These data suggest that the Hh pathway impacts on the sex determination process and vice versa and that the pathway may serve more functions than the regulation of Ci.
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, Alabama 35294, USA.
Jamila I
JI
Horabin
Sabrina
S
Walthall
Cynthia
C
Vied
Michelle
M
Moses
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004628:Embryonic Structures / Q000502:physiology; D005260:Female; D053823:Hedgehog Proteins; D007301:Insect Hormones; D016547:Kinesins / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D007301:Insect Hormones; D046911:Macromolecular Substances; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C097059:Su(fu) protein, Drosophila; C067777:Sxl protein, Drosophila; D014157:Transcription Factors; C092937:ci protein, Drosophila; C107452:cos protein, Drosophila; C070844:ptc protein, Drosophila; C077245:hh protein, Drosophila; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins