Chemical genetics reveals cross-regulation of plant developmental signaling by the immune peptide-receptor pathway

Cells sense and integrate multiple signals to coordinate a response. A receptor-kinase signaling pathway for plant stomatal development shares components with the immunity pathway. The mechanism ensuring their signal specificities remains unclear. Using chemical genetics, here, we report the identification of a small molecule, kC9, that triggers excessive stomatal differentiation by inhibiting the canonical ERECTA pathway. kC9 binds to and inhibits the downstream mitogen-activated protein kinase MPK6, perturbing its substrate interaction. Notably, activation of immune signaling by a bacterial flagellin peptide nullified kC9's effects on stomatal development. This cross-regulation depends on the immune receptor FLS2 (FLAGELLIN SENSING 2) and occurs even in the absence of kC9 if the ERECTA family receptor population becomes suboptimal. Proliferating stomatal lineage cells are vulnerable to this immune signal penetration. Our findings suggest that the signal specificity between development and immunity can be ensured by mitogen-activated protein kinase homeostasis, reflecting the availability of upstream receptors, thereby providing an unanticipated view on signal specificity.