Drosophila homeodomain protein dHb9 directs neuronal fate via crossrepressive and cell-nonautonomous mechanisms.
Here we present the identification and characterization of dHb9, the Drosophila homolog of vertebrate Hb9, which encodes a factor central to motorneuron (MN) development. We show that dHb9 regulates neuronal fate by restricting expression of Lim3 and Even-skipped (Eve), two homeodomain (HD) proteins required for development of distinct neuronal classes. Also, dHb9 and Lim3 are activated independently of each other in a virtually identical population of ventrally and laterally projecting MNs. Surprisingly, dHb9 represses Lim3 cell nonautonomously in a subset of dorsally projecting MNs, revealing a novel role for intercellular signaling in the establishment of neuronal fate in Drosophila. Lastly, we provide evidence that dHb9 and Eve regulate each other's expression through Groucho-dependent crossrepression. This mutually antagonistic relationship bears similarity to the crossrepressive relationships between pairs of HD proteins that pattern the vertebrate neural tube.
Broihier
Heather T
HT
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Skeath
James B
JB
D000818:Animals; D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D002633:Chemotaxis / Q000235:genetics; D002828:Choristoma / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C052837:eve protein, Drosophila; C490005:exex protein, Drosophila; C091023:gro protein, Drosophila