Xpbx1b and Xmeis1b play a collaborative role in hindbrain and neural crest gene expression in Xenopus embryos.
Pbx1 is a homeodomain protein that functions in complexes with other homeodomain-containing proteins to regulate gene expression during embryogenesis and oncogenesis. Pbx proteins bind DNA cooperatively as heterodimers or higher order complexes with Meis family members and Hox proteins and are believed to specify cell identity during development. Here, we present evidence that Pbx1, in partnership with Meis1b, can regulate posterior neural markers and neural crest marker genes during Xenopus development. A Xenopus homolog of the Pbx1b homeodomain protein was isolated and shown to be expressed throughout embryogenesis. Xpbx1b expression overlaps with Xmeis1 in several areas, including the lateral neural folds, caudal branchial arch, hindbrain, and optic cup. When ectopically expressed, Xpbx1b can synergize with Xmeis1b to promote posterior neural and neural crest gene expression in ectodermal explants. Further, a physical interaction between these two homeodomain proteins is necessary for induction of these genes in embryonic tissue. In addition, coexpression of Xmeis1b and Xpbx1b leads to a prominent shift in the localization of Xmeis1b from the cytoplasm to the nucleus, suggesting that nuclear transport or retention of Xmeis1b may depend upon Xpbx1b. Finally, expression of a mutant construct in which Xpbx1b protein is fused to the repressor domain from Drosophila Engrailed inhibits posterior neural and neural crest gene expression. These data indicate that Xpbx1b and its partner, Xmeis1b, function in a transcriptional activation complex during hindbrain and neural crest development.
Maeda
Ryu
R
Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702, USA.
Ishimura
Akihiko
A
Mood
Kathleen
K
Park
Eui Kyun
EK
Buchberg
Arthur M
AM
Daar
Ira O
IO
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D019281:Dimerization; D015723:Gene Library; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D009432:Neural Crest / Q000378:metabolism*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000502:physiology*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C456284:Meis1b protein, Xenopus; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C456283:PBX1 protein, Xenopus; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; C083400:PBX1 protein, human; D012313:RNA