FIGURE 1. Identification of a mouse Dscam mutation.

a, A schematic of the DSCAM protein domain structure. The extracellular portion of DSCAM consists of ten immunoglobulin-like repeats (Ig) and six fibronectin domains (FN). The Dscam deletion truncates the coding sequence in the second fibronectin domain (arrow), which is before the transmembrane and PAK1-interacting domains (PID). b, Northern blotting of mRNA purified from whole brains of wild-type (+/+), Dscam^+/- and Dscam^-/- mice revealed a 70% reduction in Dscam mRNA in the mutant sample. -actin (Actb) was used as a loading control. c–f, Haematoxylin and eosin stained sections of Dscam^-/- and wild-type retinas from P0 and adult mice. The Dscam^-/- retina is indistinguishable from that of the wild type during embryonic stages of development and at birth (c, d). INBL, innerneuroblast layer; ONBL, outerneuroblast layer; ONL, outernuclear layer; OPL, outerplexiform layer. e, f, In the adult Dscam^-/- retina, the inner nuclear (INL), inner plexiform (IPL) and retinal ganglion (RGL) layers are disorganized compared to those of the wild-type retina, whereas other retinal layers are indistinguishable from that of the wild type. g, In situ hybridization with Dscam antisense probes (Dscam AS) revealed expression in a subset of cells in the inner nuclear and ganglion cell layers. h, Whole control P15 retina stained with antibodies to DSCAM and TH. i, A section of a control adult (6–10-week-old) retina labelled using antibodies to DSCAM and TH. j, A section of wild-type P15 retina stained with DSCAM antibodies. k, A section of the Dscam^-/- retina stained with an antibody to DSCAM. Scale bars: c, d, 80 m; e, f, 106 m; g, 160 m; h, 45 m; i, 120 m; j, k, 65 m.