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EBioMedicine. 2015 Apr 18;2(6):513-27. doi: 10.1016/j.ebiom.2015.04.012. eCollection 2015 Jun.

Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.

Author information

1
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.
2
Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
3
Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany ; Institute of Molecular Biology, 55128 Mainz, Germany.

Abstract

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.

KEYWORDS:

Canonical Wnt; Grainyhead-like family; Neural fold; Neural tube closure; Neural tube defects; Surface ectoderm; Uncommitted progenitors; Wnt antagonists

Comment in

PMID:
26288816
PMCID:
PMC4535158
DOI:
10.1016/j.ebiom.2015.04.012
[Indexed for MEDLINE]
Free PMC Article

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