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Cytonemes are tendril-like appendages that developing cells use to communicate across large distances. Their cargo—including the key signaling protein Sonic Hedgehog (SHH)—is highly specific, but the mechanisms underlying this specificity were unclear.

Now, scientists at St. Jude Children's Research Hospital have revealed how SHH activates a receptor protein cascade that travels with the protein into the cytoneme. This creates a bespoke highway connecting cells during embryonic development. The study, published in Science Advances, showcases how cytonemes coordinate tissue development, with potential implications for developmental disorders and cancer.

"Cytonemes are built from actin and can grow to extraordinary lengths," said corresponding author Stacey Ogden, Ph.D., St. Jude Department of Cell & Molecular Biology. "We found evidence that Sonic Hedgehog may help direct the construction of its own long-range communication routes by recruiting receptors, which connect the signal to the actin machinery that drives cytoneme growth."

The researchers found that SHH was enlisting cytoneme "project managers" BOC and CDON, which bring in the "engineer" FARP1 and the "construction worker" Cdc42. When they removed BOC and CDON from SHH-producing cells, cytoneme numbers dropped, which affected how developing neural cells formed different cell types.

, St. Jude Graduate School of Biomedical Sciences alumna and postdoctoral research associate in the Ogden Lab, Department of Cell & Molecular Biology.

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