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Updated: Nov 8, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
Ahmad Abdullah1, Carl Herdenberg1, Håkan Hedman2,3
1Department of Radiation Sciences, Oncology, Umeå University, 90187, Umeå, Sweden.
Abstract:
Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.
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