An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development

Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by fibroblast growth factor (Fgf) signaling at the blastula margin. Here, we describe an improved Erk-specific biosensor, which we term modified Erk kinase translocation reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Erk activity is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo. [Display omitted] •Erk-KTR displays Cdk1-dependent activity that impairs Erk-specific readout•modErk-KTR represents an improved Erk-specific biosensor in zebrafish and Drosophila•Mitosis introduces periods of Erk inactivity in zebrafish and Drosophila embryos•Mitotic erasure introduces heterogeneity to Fgf signal interpretation Wilcockson et al. describe the development of an improved Erk-specific kinase translocation reporter (modErk-KTR). Live imaging of Erk dynamics in zebrafish and Drosophila embryos shows that Erk signaling is shut down prior to mitosis (mitotic erasure), which contributes to heterogeneity in Fgf signal interpretation in zebrafish embryos.