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

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Summary

Researchers developed a new biosensor to track Extracellular signal-regulated kinase (Erk) dynamics in developing embryos. This tool revealed Erk signaling is crucial for tissue growth and exhibits unique "mitotic erasure" before cell division.

Keywords:
DrosophilaErkFgf signalingkinase translocation reportermitosiszebrafish

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Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • Extracellular signal-regulated kinase (Erk) signaling dynamics influence cellular responses across various biological contexts.
  • The early zebrafish embryo serves as a valuable model for in vivo studies of Erk signaling dynamics.
  • Fibroblast growth factor (Fgf) signaling at the blastula margin induces a gradient of activated diphosphorylated Erk (P-Erk) in zebrafish embryos.

Purpose of the Study:

  • To develop and characterize an improved Erk-specific biosensor for real-time monitoring of Erk signaling dynamics.
  • To investigate the role and dynamics of Fgf/Erk signaling in tissue growth during early embryonic development in zebrafish and Drosophila.
  • To understand the phenomenon of Erk activity extinction prior to mitosis, termed mitotic erasure, and its contribution to cellular heterogeneity.

Main Methods:

  • Development of a modified Erk kinase translocation reporter (modErk-KTR) biosensor.
  • In vitro and in vivo validation of the modErk-KTR biosensor in developing zebrafish and Drosophila embryos.
  • Live imaging and analysis of Erk signaling dynamics coupled with tissue growth and cell division.

Main Results:

  • The modErk-KTR biosensor effectively visualizes Erk signaling dynamics in vitro and in vivo.
  • Fgf/Erk signaling is dynamically coupled to tissue growth in both zebrafish and Drosophila during early development.
  • Erk activity is rapidly suppressed before mitosis (mitotic erasure), creating periods of inactivity and contributing to cell division heterogeneity.

Conclusions:

  • The modErk-KTR biosensor is a powerful tool for studying Erk signaling dynamics in vivo.
  • Erk signaling plays a critical role in coordinating tissue growth with cell division timing during embryonic development.
  • Mitotic erasure represents a novel mechanism contributing to cell-to-cell variability in dividing tissues.