An FGF timer for zygotic genome activation [Research Communications]

Nicholas Treen1, Emily Chavarria2, Claire J. Weaver2, Clifford P. Brangwynne1,3,4 and Michael Levine1,2 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA; 2Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA; 3Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, USA; 4Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA Corresponding author: ntreenprinceton.edu Abstract

Zygotic genome activation has been extensively studied in a variety of systems including flies, frogs, and mammals. However, there is comparatively little known about the precise timing of gene induction during the earliest phases of embryogenesis. Here we used high-resolution in situ detection methods, along with genetic and experimental manipulations, to study the timing of zygotic activation in the simple model chordate Ciona with minute-scale temporal precision. We found that two Prdm1 homologs in Ciona are the earliest genes that respond to FGF signaling. We present evidence for a FGF timing mechanism that is driven by ERK-mediated derepression of the ERF repressor. Depletion of ERF results in ectopic activation of FGF target genes throughout the embryo. A highlight of this timer is the sharp transition in FGF responsiveness between the eight- and 16-cell stages of development. We propose that this timer is an innovation of chordates that is also used by vertebrates.

Received October 11, 2022. Accepted January 19, 2023.

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