In the spinal cord, the central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse and chick models to show that dorsal ventricular layer (dVL) cells adjacent to dorsal midline Nestin⁽⁺⁾ radial glia (dmNes⁺RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) and delaminate in a stepwise manner; live imaging shows that as one cell delaminates, the next cell ratchets up, the dmNes⁺RG endfoot ratchets down, and the process repeats. We show that dmNes⁺RG secrete a factor that promotes loss of cell polarity and delamination. This activity is mimicked by a secreted variant of Crumbs2 (CRB2S) which is specifically expressed by dmNes⁺RG. In cultured MDCK cells, CRB2S associates with apical membranes and decreases cell cohesion. Analysis of Crb2^F/F/Nestin-Cre^+/− mice, and targeted reduction of Crb2/CRB2S in slice cultures reveal essential roles for transmembrane CRB2 (CRB2TM) and CRB2S on VL cells and dmNes⁺RG, respectively. We propose a model in which a CRB2S–CRB2TM interaction promotes the progressive attrition of the dVL without loss of overall VL integrity. This novel mechanism may operate more widely to promote orderly progenitor delamination.

在脊髓中，中央管通过称为背侧塌陷的知之甚少的过程形成，该过程涉及假复层心室层 (VL) 细胞的磨损和重塑。在这里，我们使用小鼠和小鸡模型显示与背中线巢蛋白⁽⁺⁾放射状胶质细胞 (dmNes ⁺ RG) 相邻的背心室层 (dVL) 细胞下调顶端极性蛋白，包括 Crumbs2 (CRB2) 并逐步分层方式; 实时成像显示，当一个细胞分层时，下一个细胞会向上棘轮，dmNes ⁺ RG 端足棘轮向下，并且该过程重复。我们证明了 dmNes ⁺RG 分泌一种促进细胞极性丧失和分层的因子。该活动由 dmNes ⁺ RG 特异性表达的 Crumbs2 (CRB2S) 的分泌变体模拟。在培养的 MDCK 细胞中，CRB2S 与顶膜结合并降低细胞凝聚力。对Crb2 ^F/F /Nestin-Cre ^+/-小鼠的分析以及切片培养物中Crb2 /CRB2S 的靶向还原揭示了跨膜 CRB2 (CRB2TM) 和 CRB2S 对 VL 细胞和 dmNes ^{+的重要作用}RG，分别。我们提出了一个模型，其中 CRB2S-CRB2TM 相互作用促进了 dVL 的逐步磨损，而不会损失整体 VL 完整性。这种新颖的机制可以更广泛地运作以促进有序的祖细胞分层。