Xenopus XsalF: anterior neuroectodermal specification by attenuating cellular responsiveness to Wnt signaling.
Here we show that XsalF, a frog homolog of the Drosophila homeotic selector spalt, plays an essential role for the forebrain/midbrain determination in Xenopus. XsalF overexpression expands the domain of forebrain/midbrain genes and suppresses midbrain/hindbrain boundary (MHB) markers and anterior hindbrain genes. Loss-of-function studies show that XsalF is essential for the expression of the forebrain/midbrain genes and for the repression of the caudal genes. Interestingly, XsalF functions by antagonizing canonical Wnt signaling, which promotes caudalization of neural tissues. XsalF is required for anterior-specific expressions of GSK3beta and Tcf3, genes encoding antagonistic effectors of Wnt signaling. Loss-of-function phenotypes of GSK3beta and Tcf3 mimic those of XsalF while injections of GSK3beta and Tcf3 rescue loss-of-function phenotypes of XsalF. These findings suggest that the forebrain/midbrain-specific gene XsalF negatively controls cellular responsiveness to posteriorizing Wnt signals by regulating region-specific GSK3beta and Tcf3 expression.
Onai
Takayuki
T
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Sasai
Noriaki
N
Matsui
Masaru
M
Sasai
Yoshiki
Y
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D029721:Drosophila Proteins; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000071679:Glycogen Synthase Kinase 3 beta; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics
D018076:DNA, Complementary; D029721:Drosophila Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C488978:SALL2 protein, Xenopus; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; C085793:salm protein, Drosophila; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3