TY - JOUR T1 - Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101100 VL - 4 IS - 11 SP - e202101100 AU - Theresa Rauschendorfer AU - Selina Gurri AU - Irina Heggli AU - Luigi Maddaluno AU - Michael Meyer AU - Álvaro Inglés-Prieto AU - Harald Janovjak AU - Sabine Werner Y1 - 2021/11/01 UR - https://www.life-science-alliance.org/content/4/11/e202101100.abstract N2 - FGFs and their high-affinity receptors (FGFRs) play key roles in development, tissue repair, and disease. Because FGFRs bind overlapping sets of ligands, their individual functions cannot be determined using ligand stimulation. Here, we generated a light-activated FGFR2 variant (OptoR2) to selectively activate signaling by the major FGFR in keratinocytes. Illumination of OptoR2-expressing HEK 293T cells activated FGFR signaling with remarkable temporal precision and promoted cell migration and proliferation. In murine and human keratinocytes, OptoR2 activation rapidly induced the classical FGFR signaling pathways and expression of FGF target genes. Surprisingly, multi-level counter-regulation occurred in keratinocytes in vitro and in transgenic mice in vivo, including OptoR2 down-regulation and loss of responsiveness to light activation. These results demonstrate unexpected cell type–specific limitations of optogenetic FGFRs in long-term in vitro and in vivo settings and highlight the complex consequences of transferring optogenetic cell signaling tools into their relevant cellular contexts. ER -