Abstract
Pulsatile activity of the extracellular signal-regulated kinase (ERK) controls several cellular, developmental, and regenerative programs. Sequential segmentation of somites along the vertebrate body axis, a key developmental program, is also controlled by ERK activity oscillation. The oscillatory expression of Her/Hes familytranscription factors constitutes the segmentation clock, setting the period of segmentation. Although oscillation of ERK activity depends on Her/Hes proteins, the underlying molecular mechanism remained mysterious. Here, we show that Her/Hes proteins physically interact with and stabilize dual-specificity phosphatases (Dusp) of ERK, resulting in oscillations of Dusp4 and Dusp6 proteins. Pharmaceutical and genetic inhibition of Dusp activity disrupt ERK activity oscillation and somite segmentation in zebrafish. Our results demonstrate that post-translational interactions of Her/Hes transcription factors with Dusp phosphatases establish the fundamental vertebrate body plan. We anticipate that future studies will identify currently unnoticed post-translational control of ERK pulses in other systems.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
