Author: ["James Cooley","Stacia Whitaker","Sarah Sweeney","Scott Fraser","Brad Davidson"]
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Abstract
Cardiac fate choices in Ciona intestinalis depend on the CDC42-mediated formation of invasive protrusions that probe for inductive signals in the environment. Cells must make appropriate fate decisions within a complex and dynamic environment1. In vitro studies indicate that the cytoskeleton acts as an integrative platform for this environmental input2. External signals regulate cytoskeletal dynamics and the cytoskeleton reciprocally modulates signal transduction3,4. However, in vivo studies linking cytoskeleton/signalling interactions to embryonic cell fate specification remain limited5,6,7. Here we show that the cytoskeleton modulates heart progenitor cell fate. Our studies focus on differential induction of heart fate in the basal chordate Ciona intestinalis. We have found that differential induction does not simply reflect differential exposure to the inductive signal. Instead, pre-cardiac cells employ polarized, invasive protrusions to localize their response to an ungraded signal. Through targeted manipulation of the cytoskeletal regulator CDC42, we are able to depolarize protrusive activity and generate uniform heart progenitor fate specification. Furthermore, we are able to restore differential induction by repolarizing protrusive activity. These findings illustrate how bi-directional interactions between intercellular signalling and the cytoskeleton can influence embryonic development. In particular, these studies highlight the potential for dynamic cytoskeletal changes to refine cell fate specification in response to crude signal gradients.Cite this article
Cooley, J., Whitaker, S., Sweeney, S. et al. Cytoskeletal polarity mediates localized induction of the heart progenitor lineage. Nat Cell Biol 13, 952–957 (2011). https://doi.org/10.1038/ncb2291 