Fig. 1. A comprehensive and conserved network of BM zone genes.

(A) Strategy for identifying putative BM matrix protein and CSI genes in humans and other species. Protein localization to BM zone was either (i) confirmed through vertebrate tissue immunolocalization (green column) or (ii) predicted on the basis of BM protein interaction or BM-cleaving protease activity (magenta column). Fluorescent tagging studies in C. elegans provided further localization support for components in both columns. Genes with insufficient evidence are in the gray column. *160 components are localized to the human BM zone. (B) Top: Schematic representation of the pharyngeal and gonadal BMs in C. elegans (Biorender). Middle: Confocal mid-plane z-slices of adult animals expressing endogenously tagged COL4A1/EMB-9::mRuby2. Bottom: Selected BM zone candidates tagged with mNG in this study. BM zone localization in respective tissues is indicated by yellow (pharynx and gonad), blue (body wall muscle), and green (nerve ring) arrowheads. Asterisks denote punctate intracellular signal within body wall muscle tissue, a major site of BM protein synthesis. †MATN1 is a predicted human candidate and its ortholog localized to the BM zone in C. elegans. #Localization evidence present for two of four UNC5, one of three SPOCK, and one of four ROBO family members in humans (table S7). Scale bars, 25 μm. (C) Integrated BM zone network of 222 human genes (circles, 160 BM matrix and 62 CSI components) with corresponding C. elegans orthologs (octagons). Lines link ortholog pairs. Boxes indicate number of ortholog genes in mouse, zebrafish, Drosophila, and C. elegans. *Complex ortholog families in C. elegans (detailed in fig. S4). †Duplicated zebrafish genes were counted as one; worm §astacins and #tetraspanins are not included. Network is curated at https://bmbase.manchester.ac.uk/.