Distributing signaling proteins in space and time: the province of cytonemes

Abstract

During development, cells use specialized filopodia called cytonemes to deploy the signaling proteins that coordinate growth and direct morphogenesis. Cytonemes are dynamic structures that can extend long distances across tissues to either deliver or take up signaling proteins. Signaling proteins transfer between cells at the tips of cytonemes where specific contacts termed morphogenetic synapses form. This review summarizes our current understanding of the roles and functions of cytonemes, and it explores some of the conceptual issues relevant to the cytoneme mechanism of contact-dependent cell-cell signaling.

Figure 1. Experimental addition of unbound signal

(A) Placement of a bead soaked with PBS+FGF induces pax9 expression in surrounding cells (right), in contrast to a bead soaked with only PBS (left). (from [48]) (B) Cells in a brain slice respond to neurotransmitter added by pipet.

Figure 2. Surface diffusion model of signal protein dispersion

Movement (left to right) of signaling protein (red) across a sheet of cells with HSPGs (green column with blue strands) and receptor (black) on the cell surface is hypothesized to repeat cycles of binding to an HSPG, release and random walk, with eventual binding to receptor and uptake.

Figure 3. Cytonemes of normal and mutant cells

(A, B) Cytonemes extend across “intermediate cells” (gray), linking cells (green) that produce signal (red) with cells (beige) that receive signal. (C) Receiving cells that lack Neuroglian (Nrg), diaphanous (dia), shibire (shi), myospheroid (mys), multiple edematous wings (mew) or inflated (if) do not have cytonemes. (D) Receiving cells that lack Capricious (Caps) extend cytonemes that do not contact producing cells. (E) Cytonemes do not extend across intermediate cells that lack dally, dally-like, prickled (pk), Van Gogh (Vang), Grunge (Gug) or wing blister (wb). (F) Producing cells that lack SCAR, Capping protein a (cpa) or pico do not extend cytonemes.