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. 2022 May 19;13:2785. doi: 10.1038/s41467-022-30466-6

Fig. 8. Proposed model for NF1 mutation-induced, neuronal hyperexcitability-regulated low-grade tumor growth.

Fig. 8

A Tumor-associated NF1-mutant sensory neurons have increased baseline neuron excitability and deregulated HCN channel function, leading to elevated COL1A2 secretion. COL1A2, in turn, increases NF1−/− Schwann cell proliferation to stimulate pNF growth. B Tumor-associated NF1-mutant retinal ganglion cell (RGC) activity is governed by two distinct mechanisms. First, visual experience (light)-induced activity enhances RGC production of soluble-Nlgn3 (s-Nlgn3), which drives OPG initiation and cell growth. Second, tumor-associated NF1-mutant RGCs have increased intrinsic baseline neuronal hyperexcitability, which is controlled by HCN channel function. Increased baseline HCN channel-regulated RGC excitability triggers increased midkine production to induce a T-cell (Ccl4) and microglial (Ccl5) signaling cascade that governs OPG progression and growth. PNS, peripheral nervous system, CNS, central nervous system, pNF, plexiform neurofibroma, OPG, optic pathway glioma. Small elements of this schematic were designed on BioRender.com. Source data are provided as a Source Data file.