Fig. 9.

A schematic model of fate specification of uncommitted progenitors in the neural plate border/neural folds being coordinately coupled to neural tube closure. (A) A schematic model illustrating an intimate link between fate specification of the uncommitted progenitor cells and neural tube closure. Prior to the fusion of neural folds, the neural plate border cells between the NE (in blue) and SE (in yellow), which express DKK1/KREMEN1 (in red), are not specified into either the NE or SE fate as an uncommitted progenitor state marked by OCT4, KLF5 and SSEA4 (upper illustration). During the progression of neural tube closure, GRHL3-positive cells (in green) directed by canonical Wnt emerge coordinately in the vicinity of the neural plate border toward the identical direction of the neuropore closure, and then DKK1/KREMEN1-positive cells (in red) become restricted to the opposite side, where the neuropore is still open (lower illustration). (B) At the midline fusion of the neural folds, neural plate border cells lose the stem cell-like character and progressively specify into either SE or NE, regulated by canonical Wnt and its antagonists, respectively. In the Grhl3^{cre-nZ/cre-nZ} and β-catenin conditional knockout embryos, uncommitted progenitor cells are expanded in the neural plate border and consequently they result in hyperplasia of NE with hypoplasia of SE, and consequently, the neural tube fails to close correctly.