Neural crest FGF signaling controls lacrimal gland development

Summary Neural crests are multipotent progenitors that migrate from the neural tube to populate the entire body, differentiating into diverse cell types in many organs. FGF signaling is one of the key regulators of neural crest development, but the downstream signaling mechanism is not well understood. Here we show that conditional knockout of Shp2 disrupted migration, survival and differentiation of neural crests, culminating in the loss of Fgf10 into the periocular mesenchyme. This results in abrogation of lacrimal gland development. These phenotypes are reproduced by genetic ablation of Fgfr, adaptor protein Frs2 and downstream kinases Mek and Erks in the neural crest, and rescued by constitutive activation of Kras, establishing a FGFR ‐Frs2‐Shp2‐Ras‐ MEK ‐ ERK cascade. By RNA seq analysis, we showed that Shp2 deficiency causes significant changes in the neural crest transcriptome and identified critical regulator of Fgf10 expression in the periocular mesenchyme. These results demonstrate that neural crest FGF signaling is essential for lacrimal gland induction.