Journal
JOURNAL OF CELL BIOLOGY
Volume 198, Issue 5, Pages 941-952Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201203012
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Funding
- National Institutes of Health [T32HL007731, K01DK092312, GM084040, DK60322]
- California Institute for Regenerative Medicine [TG2-01153]
- Packard Foundation D.Y.R. Stainier
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Embryo morphogenesis is driven by dynamic cell behaviors, including migration, that are coordinated with fate specification and differentiation, but how such coordination is achieved remains poorly understood. During zebrafish gastrulation, endodermal cells sequentially exhibit first random, nonpersistent migration followed by oriented, persistent migration and finally collective migration. Using a novel transgenic line that labels the endodermal actin cytoskeleton, we found that these stage-dependent changes in migratory behavior correlated with changes in actin dynamics. The dynamic actin and random motility exhibited during early gastrulation were dependent on both Nodal and Rac1 signaling. We further identified the Rac-specific guanine nucleotide exchange factor Prex1 as a Nodal target and showed that it mediated Nodal-dependent random motility. Reducing Rac1 activity in endodermal cells caused them to bypass the random migration phase and aberrantly contribute to mesodermal tissues. Together, our results reveal a novel role for Nodal signaling in regulating actin dynamics and migration behavior, which are crucial for endodermal nnorphogenesis and cell fate decisions.
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