Mutations of WD40 repeat domain 60 (WDR60) have been identified in short-rib polydactyly syndromes (SRPS I–V), a group of lethal congenital disorders characterized by short ribs, polydactyly, and a range of extraskeletal phenotypes. However, the underlying mechanism is still unclear. Here, we report that WDR60 is essential for embryonic development and plays a critical role in the multipolar-bipolar transition and migration of newborn neurons during brain development. Mechanically, we found that WDR60 was located at the microtubule-organizing center to control microtubule organization and possibly, the trafficking of cellular components. Importantly, the migration defect caused by Wdr60 knockdown could be rescued by the stable form of α-Tubulin, α-Tubulin^K40Q (an acetylation-mimicking mutant). These findings identified a non-cilia function of WDR60 and provided insight into its biological function, as well as the pathogenesis of WDR60 deficiency associated with SRPS.

WD40 重复结构域 60 ( WDR60 ) 的突变已在短肋多指综合征 (SRPS I-V) 中发现，这是一组以短肋、多指和一系列骨骼外表型为特征的致命先天性疾病。然而，其潜在机制仍不清楚。在这里，我们报告 WDR60 对胚胎发育至关重要，并且在大脑发育过程中新生神经元的多极-双极转换和迁移中起着关键作用。从机制上讲，我们发现 WDR60 位于微管组织中心，以控制微管组织，并可能控制细胞成分的运输。重要的是，由Wdr60敲低引起的迁移缺陷可以通过稳定形式的 α-微管蛋白，α-微管蛋白^{K40Q 来挽救}（乙酰化模拟突变体）。这些发现确定了 WDR60 的非纤毛功能，并提供了对其生物学功能的洞察，以及与 SRPS 相关的 WDR60 缺陷的发病机制。