Editors' ChoiceDevelopment

Getting to the Heart of the Matter

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Science Signaling  09 Aug 2011:
Vol. 4, Issue 185, pp. ec222
DOI: 10.1126/scisignal.4185ec222

During heart development, precursor cells must integrate signals from the surrounding macro- and microenvironments and respond in an accurate manner to undergo induction to the appropriate cell fate. In the model organism Ciona intestinalis, “founder” cells divide asymmetrically to produce heart lineage precursor and tail muscle precursor cells. Using this primitive chordate, Cooley et al. found that the founder cells formed polarized, invasive protrusions and that the side of the cell with the protrusions differentiated into the heart lineage precursors after asymmetric division. The protrusions enabled the cells to generate a localized response to a relatively ungraded fibroblast growth factor (FGF) signal, a key growth factor in specifying the heart progenitor lineage. In situ hybridization and immunohistochemistry indicated that the Ciona founder cells are surrounded by FGF-expressing cells in the adjacent mesenchyme and are initially exposed to uniform amounts of FGF, a pattern that persists until after the initial founder cell asymmetric division. Time-lapse imaging of living embryos revealed, however, that just before this asymmetric division the founder cells extended invasive protrusions into the underlying ventral epidermis. These founder cell protrusions were localized along the cell membrane region from which the heart progenitor cells would emerge (the anterior-ventral edge). Fluorescence images of fixed embryos at a similar developmental stage indicated that F-actin and FGF receptor activation also became concentrated at the anterior-ventral edge of the membrane of the presumptive heart progenitor cells. The polarized protrusive activity, F-actin cortical concentration, and FGF receptor activation correlated with induction of the heart progenitor cell fate but not with the initiation of heart progenitor cell migration, which occurs at later developmental stages. Disruption of localized actin dynamics in founder cells through expression of a constitutively active mutant of the small guanosine triphosphatase Cdc42, a regulator of actin dynamics, driven by a mesoderm posterior (Mesp) enhancer element led to more uniform extension of cell protrusions from regions of the cell surface and an expansion of heart marker gene expression to all founder lineage cells. Similar effects were not seen upon targeted expression of wild-type Cdc42 in founder cells. Together, the authors suggest that polarized cytoskeletal dynamics and protrusive membranes can facilitate localized signal transduction, including in the context of relatively uniform growth factor receptor occupancy and subsequent cell fate specification.

J. Cooley, S. Whitaker, S. Sweeney, S. Fraser, B. Davidson, Cytoskeletal polarity mediates localized induction of the heart progenitor lineage. Nat. Cell Biol. 13, 952–957 (2011). [PubMed]

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