Anteroposterior Wnt-RA Gradient Defines Adhesion and Migration Properties of Neural Progenitors in Developing Spinal Cord

Abstract

Mammalian embryos exhibit a transition fromheadmorphogenesis to trunk elongation tomeet the demand of axial elongation. The caudal neural tube (NT) is formedwith neural progenitors (NPCs) derived fromneuromesodermal progenitors localized at the tail tip. However, the molecular and cellular basis of elongatingNTmorphogenesis is yet elusive. Here, we provide evidence that caudalNPCs exhibit strong adhesion affinity that is gradually decreased along the anteroposterior (AP) axis in mouse embryonic spinal cord and human cellular models. Strong cell-cell adhesion causes collective migration, allowing AP alignment of NPCs depending on their birthdate. We further validated that this axial adhesion gradient is associated with the extracellular matrix and is under the control of graded Wnt signaling emanating from tail buds and antagonistic retinoic acid (RA) signaling. These results suggest that progressive reduction of NPC adhesion along the AP axis is under the control of Wnt-RA molecular networks, which is essential for a proper elongation of the spinal cord.