Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.
During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. Our results also demonstrated that canonical Wnt and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into SE or NE fates in accord with the progress of neural tube closure. Additionally, SE specification of the neural plate border via canonical Wnt signaling is directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose that the fate specification of uncommitted progenitors in the neural plate border by canonical Wnt signaling and its downstream effector Grhl3 is crucial for neural tube closure. This study implicates that failure in critical genetic factors controlling fate specification of progenitor cells in the neural plate border/neural fold coordinated with neural tube closure may be potential causes of human neural tube defects.
Department of Molecular Embryology, Osaka Medical Center, Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
Chiharu
C
Kimura-Yoshida
Department of Molecular Embryology, Osaka Medical Center, Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
Kyoko
K
Mochida
Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
Kristina
K
Ellwanger
Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany ; Institute of Molecular Biology, 55128 Mainz, Germany.
Christof
C
Niehrs
Department of Molecular Embryology, Osaka Medical Center, Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
Isao
I
Matsuo
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004475:Ectoderm / Q000196:embryology; D046149:Embryo Culture Techniques; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000196:embryology*; D054258:Neural Plate / Q000196:embryology*; D058953:Neural Stem Cells / Q000166:cytology; D054261:Neurulation / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics
D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C501127:Dkk1 protein, mouse; C473143:GRHL3 protein, human; C486077:Kremen1 protein, mouse; C527933:Sox9 protein, mouse
Canonical Wnt; Grainyhead-like family; Neural fold; Neural tube closure; Neural tube defects; Surface ectoderm; Uncommitted progenitors; Wnt antagonists