Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

颅面形态发生需要咽弓和支气管上膜的适当发育。我们显示，除了引起颅内感觉神经元外，支气管上前庭产生小鼠咽弓发育的新型谱系相关的非神经元细胞群体。Eya1对于发展支气管上的前庭和近端咽弓是必不可少的。我们确定了一个Eya1-Notch调控轴，该轴指定了支气管上膜的神经元和非神经元承诺，其中Notch在Eya1下游起作用并促进了非神经元细胞命运。Notch受Eya1的苏氨酸磷酸酶活性调节。Eya1对Notch1细胞内结构域（Notch1 ICD）的p-苏氨酸2122进行去磷酸化，可以增加Notch1 ICD的稳定性，并在非神经支气管上睑板腺细胞中维持Notch信号传导活性。我们的数据揭示了在支气管上膜中更复杂的分化程序，以及Eya1-Notch轴在颅面形态发生中的重要作用。