ADAM17 regulates neurite outgrowth and visual system development with effects spanning optic vesicle morphogenesis to eye tracking
MacLeod, Collin
MacLeod, Collin
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Abstract
A disintigrin and metalloprotease 17 (ADAM17 is best understood for shedding the ectodomains of inflammatory and growth factor signaling ligands and receptors. Here we identify ADAM17 as a key developmental regulator of neurite outgrowth and functional visual system assembly. Pharmacological inhibition of ADAM17 in N1E-115 mouse retinoblastoma cells increased neurite outgrowth and development. Through quantitative proteomics, we identify ADAM17 substrates suppressing neurite outgrowth in N1E-115 cells as eight established and eight novel substrates, the majority of which are guidance and adhesion molecules. Identified ADAM17 substrates are expressed within both mouse retinal precursor and retinal ganglion cells (RGCs). ADAM17 protein domains are widely conserved across vertebrates, with zebrafish adam17a/b mRNA widely expressed in the developing nervous system. CRISPR-Cas9 microinjections directed to adam17a/b of zebrafish embryos leads to smaller optic vesicles and poorer tissue separation, as well as impaired visual relay center innervation by RGCs. These morphological impairments persist and result in functional visual system deficits as measured by horizontal eye tracking and optokinetic response. Together, our findings suggest a role for ADAM17 as a key regulator of visual system development spanning optic vesicle, neurite, and retinal ganglion cell projection development, ultimately affecting visual output.
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Date
1/1/2026
Student Status
Graduate Student
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Poster
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Neuroscience
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College of Arts and Sciences
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Life Science