Editors' ChoiceDevelopmental Biology

Cells Concentrate to Form Organs

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Science Signaling  18 Nov 2014:
Vol. 7, Issue 352, pp. ec319
DOI: 10.1126/scisignal.aaa2954

Secreted fibroblast growth factors (FGFs) are required for proper formation of the mechanosensory lateral line organs of zebrafish. These organs are formed by rosette-shaped groups of about 20 cells that are deposited at stereotyped intervals along the anteroposterior axis by a larger group of lateral line precursor cells (the primordium) as it migrates from the head of the embryo toward the tail. Rosettes form at the rear of the primordium and drop off the primordium as it migrates posteriorly. Durdu et al. report that the architecture of these rosettes directly influences the signaling that controls when they drop out of the primordium. Genetically or pharmacologically reducing FGF signaling in vivo delayed rosette deposition, increasing the distance between organs. Overexpressing Fgf3 accelerated organ deposition, leading to more closely spaced organs, but did not affect rosette formation or the forward velocity of the migrating primordium. Time-lapse imaging revealed that fluorescently tagged Fgf3 (GFP-Fgf3), expressed at physiologically relevant concentrations, accumulated in microlumina at the center of each rosette just before the rosette arrested its migration to separate from the moving primordium. Overexpressing GFP-Fgf3 in randomly positioned clones of cells within the primordium caused GFP-Fgf3 to accumulate only in the microlumina of the rosettes with which the cells were associated.

Rosettes containing GFP-Fgf3–overexpressing cells dropped off the primordium prematurely without affecting the timing with which neighboring rosettes lacking any GFP-Fgf3–overexpressing cells dropped off the primordium. Genetically interfering with epithelial polarity prevented the accumulation of GFP-Fgf3 in microlumina, and GFP-Fgf3 leaked from microlumina punctured with a laser, delaying desposition of the rosette. The authors suggest that concentrating FGFs in microlumina allows cell behaviors within a rosette to be coordinated and may serve as a checkpoint to ensure that rosettes form properly polarized organ precursors before leaving the primordium. Whether other self-organizing cells that form central lumina use a similar mechanism to coordinate cellular behavior is an unanswered question (see commentary by Sharpe).

S. Durdu, M. Iskar, C. Revenu, N. Schieber, A. Kunze, P. Bork, Y. Schwab, D. Gilmour, Luminal signalling links cell communication to tissue architecture during organogenesis. Nature 515, 120–124 (2014). [PubMed]

J. Sharpe, Cells unite by trapping a signal. Nature 515, 41–42 (2014). [PubMed]