The secreted glycoprotein netrin-1 gained its fame as a neuronal guidance molecule. Now this molecule has moved on to the mammary gland. Srinivasan et al. report that netrin-1 acts as a sort of molecular glue for cells in buds at the growing tips of the gland (shown here as a whole mount stained with β-galactosidase, captured with light microscopy). These buds form during the equivalent of puberty in the mouse, growing as fast as 0.5 mm per day from the nipple down into a fat pad. A group of multipotent cells that strain forward at the tip of the bud express a netrin receptor, neogenin, report the investigators in the March issue of Developmental Cell. Nestled behind these cells at the tip is a separate layer of cells, which, the authors found, express netrin-1. Netrin-1–neogenin interactions seem to keep the two cell layers next to each other—and prevent the multipotent cells at the tip from wandering away. Such wandering occurs in glands lacking either netrin or neogenin, leading to cell death for some of the wayward cells. Developmental processes during adulthood may also involve netrin and neogenin, speculate the investigators, who found neogenin and netrin expressed during pregnancy and lactation. They are now taking a close look at whether loss of these genes leads to cancer susceptibility. Neogenin already has a well-known but inscrutable relative with cancer connections, DCC (deleted in colorectal carcinoma).
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Schubert, C. Breaking away from the breast. Nat Med 9, 392 (2003). https://doi.org/10.1038/nm0403-392