DEAD-Box Helicase 3 X-Linked (DDX3X) is frequently mutated in the Wingless (WNT) and Sonic hedghog (SHH) subtypes of medulloblastoma—the commonest malignant childhood brain tumor, but whether DDX3X functions as a medulloblastoma oncogene or tumor suppressor gene is not known. Here, we show that Ddx3x regulates hindbrain patterning and development by controlling Hox gene expression and cell stress signaling. In mice predisposed to Wnt- or Shh medulloblastoma, Ddx3x sensed oncogenic stress and suppressed tumor formation. WNT and SHH medulloblastomas normally arise only in the lower and upper rhombic lips, respectively. Deletion of Ddx3x removed this lineage restriction, enabling both medulloblastoma subtypes to arise in either germinal zone. Thus, DDX3X is a medulloblastoma tumor suppressor that regulates hindbrain development and restricts the competence of cell lineages to form medulloblastoma subtypes.

DEAD-Box 解旋酶 3 X 连锁 ( DDX3X ) 在髓母细胞瘤的 Wingless (WNT) 和 Sonic hedghog (SHH) 亚型（最常见的恶性儿童脑肿瘤）中经常发生突变，但DDX3X是否作为髓母细胞瘤癌基因或抑癌基因起作用，目前还不清楚。不知道。在这里，我们证明Ddx3x通过控制Hox基因表达和细胞应激信号来调节后脑模式和发育。在易患 Wnt 或 Shh 髓母细胞瘤的小鼠中， Ddx3x感知致癌应激并抑制肿瘤形成。 WNT 和 SHH 髓母细胞瘤通常分别仅出现在下菱形唇和上菱形唇。 Ddx3x的缺失消除了这种谱系限制，使得两种髓母细胞瘤亚型都出现在任一生发区。因此， DDX3X是一种髓母细胞瘤肿瘤抑制因子，可调节后脑发育并限制细胞谱系形成髓母细胞瘤亚型的能力。