Fig. S1.

Working model of gene-disease network in cartilage and spondylolysis. IPA analysis (www.ingenuity.com) was used to explore the relations of spondylolysis-causal genes (Table S7) that are expressed in developing lumbar (nodes in orange color) and interacting molecules (nodes in light blue). Their encoded proteins are either interconnected directly (solid line) or indirectly (dashed line) according to IPA and IntAct database. Estradiol, denoted by a green node, has been previously demonstrated to regulate bone and cartilage development through (A) anion transporter SLC26A2 and (B) GDF5 involved TGF-β pathway. Like the SLC26A2 (Fig. 4 A and E), GDF5 is also expressed in (C) developing lumbosacral region (EURExpress, www.eurexpress.org/ee/ and GenPaint, www.genepaint.org/) as well as in (D) spinal cartilage and soft tissues surrounding spinal cord of the juvenile mouse at four days of age (Allen Spinal Cord Atlas, mousespinal.brain-map.org/about.html). The axial lumbosacral region is indicated by arrows.