Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development.
In vertebrate embryos, formation of anterior neural structures requires suppression of Wnt signals emanating from the paraxial mesoderm and midbrain territory. In Six3(-/-) mice, the prosencephalon was severely truncated, and the expression of Wnt1 was rostrally expanded, a finding that indicates that the mutant head was posteriorized. Ectopic expression of Six3 in chick and fish embryos, together with the use of in vivo and in vitro DNA-binding assays, allowed us to determine that Six3 is a direct negative regulator of Wnt1 expression. These results, together with those of phenotypic rescue of headless/tcf3 zebrafish mutants by mouse Six3, demonstrate that regionalization of the vertebrate forebrain involves repression of Wnt1 expression by Six3 within the anterior neuroectoderm. Furthermore, these results support the hypothesis that a Wnt signal gradient specifies posterior fates in the anterior neural plate.
Lagutin
Oleg V
OV
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Zhu
Changqi C
CC
Kobayashi
Daisuke
D
Topczewski
Jacek
J
Shimamura
Kenji
K
Puelles
Luis
L
Russell
Helen R C
HR
McKinnon
Peter J
PJ
Solnica-Krezel
Lilianna
L
Oliver
Guillermo
G
D000818:Animals; D004475:Ectoderm / Q000502:physiology; D005136:Eye Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016548:Prosencephalon / Q000002:abnormalities / Q000196:embryology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins; D000097607:Homeobox Protein SIX3
D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D000097607:Homeobox Protein SIX3; C495246:Wnt1 protein, mouse; C094522:wnt8b protein, zebrafish