The functional properties of mucosal surfaces are dependent on establishing the correct proportions of specialized epithelial cell types. Multiciliated cells (also known as ciliated cells) are evolutionarily conserved and functionally indispensable epithelial cells, as suggested by the link between ciliated cell dysfunction and chronic human disease. Ciliated cell differentiation is an ordered process that involves initial cell fate determination and multiciliogenesis. STK11, a serine/threonine kinase, has been reported to be downregulated in human diseases associated with ciliopathies and functions as a tumor suppressor. Here, we show that STK11 is a physiological factor for the normal program of ciliated cell differentiation by phosphorylating MARK3, which directly suppresses ERK1/2 mediated pRB inactivation. Loss of Stk11 in airway progenitors impairs the differentiation of ciliated cells in both embryonic and adult airways. Our study establishes that STK11/MARK3/ERK1/2 signaling cascade is a key regulator to integrate ciliated cell fate commitment and the subsequent process of multiciliogenesis.

粘膜表面的功能特性取决于建立特殊上皮细胞类型的正确比例。多纤毛细胞（也称为纤毛细胞）是进化上保守且功能上不可或缺的上皮细胞，正如纤毛细胞功能障碍与人类慢性疾病之间的联系所表明的那样。纤毛细胞分化是一个有序的过程，涉及初始细胞命运决定和多纤毛发生。 STK11 是一种丝氨酸/苏氨酸激酶，据报道在与纤毛病相关的人类疾病中表达下调，并起到肿瘤抑制因子的作用。在这里，我们证明 STK11 是通过磷酸化 MARK3 来维持纤毛细胞分化正常程序的生理因子，MARK3 直接抑制 ERK1/2 介导的 pRB 失活。气道祖细胞中Stk11的缺失会损害胚胎和成人气道中纤毛细胞的分化。我们的研究证实 STK11/MARK3/ERK1/2 信号级联是整合纤毛细胞命运承诺和随后的多纤毛发生过程的关键调节因子。