Oriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divisions that are robustly oriented along the animal-vegetal embryonic axis. Here, we use a combination of lipidomics, metabolic tracer analysis and quantitative image analysis to show that sphingolipids mediate spindle positioning during oriented division of epiblast cells. We identify the Wnt signaling as a regulator of sphingolipid synthesis that mediates the activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid production. Sphingolipids determine the palmitoylation state of the Anthrax receptor, which then positions the mitotic spindle of dividing epiblast cells. Our data show how Wnt signaling mediates sphingolipid-dependent oriented division and how sphingolipids determine Anthrax receptor palmitoylation, which ultimately controls the activation of Diaphanous to mediate spindle rotation and oriented mitosis.

定向细胞分裂是控制不对称干细胞分裂，神经管延伸和体轴延伸等其他过程的基本机制。在斑马鱼胃气化过程中，当体轴延伸时，背侧成骨细胞会显示出沿着动物-植物胚胎轴稳健定向的分裂。在这里，我们使用脂质组学，代谢示踪剂分析和定量图像分析的组合来显示鞘脂在表皮细胞定向分裂过程中介导纺锤体定位。我们确定Wnt信号作为鞘脂合成的调节剂，介导丝氨酸棕榈酰转移酶（SPT），鞘脂生产中的第一个和限速酶的活性。鞘脂决定炭疽受体的棕榈酰化状态，然后将分裂的成骨细胞的有丝分裂纺锤体定位。我们的数据显示Wnt信号如何介导鞘脂依赖性定向分裂以及鞘脂如何确定炭疽受体棕榈酰化，而后者最终控制了透照的活化以介导纺锤体旋转和定向有丝分裂。