Mammalian embryos exhibit a transition from head morphogenesis to trunk elongation to meet the demand of axial elongation. The caudal neural tube (NT) is formed with neural progenitors (NPCs) derived from neuromesodermal progenitors localized at the tail tip. However, the molecular and cellular basis of elongating NT morphogenesis is yet elusive. Here, we provide evidence that caudal NPCs 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.

哺乳动物胚胎表现出从头部形态发生到躯干伸长的转变，以满足轴向伸长的需求。尾神经管 (NT) 由源自位于尾尖的神经中胚层祖细胞的神经祖细胞 (NPC) 形成。然而，延长 NT 形态发生的分子和细胞基础尚不清楚。在这里，我们提供的证据表明，在小鼠胚胎脊髓和人类细胞模型中，尾部 NPC 表现出很强的粘附亲和力，并且沿着前后（AP）轴逐渐降低。强大的细胞间粘附力会导致集体迁移，从而使 NPC 根据其出生日期进行 AP 对齐。我们进一步验证了这种轴向粘附梯度与细胞外基质相关，并且受到尾芽发出的分级 Wnt 信号和拮抗性视黄酸 (RA) 信号的控制。这些结果表明，NPC 沿着 AP 轴的粘附逐渐减少是在 Wnt-RA 分子网络的控制下，这对于脊髓的适当伸长至关重要。