Fig. 7

Partial loss of Rac1 in the retina leads to a cell-autonomous loss of retinal ganglion cell projections to retino-recipient targets in the brain. a Rac1 inactivation in the peripheral retina by Pax6α-Cre results in an optic nerve that is reduced approximately twofold in diameter and an inner plexiform layer (IPL) that is modestly reduced in thickness. Pax6α-Cre;Rac1 ^CKO/− retinas show the normal two tiers of intraretinal capillaries (IB4 staining), and GABAergic (GAD), cholinergic (ChAT), dopaminergic [i.e., tyrosine hydroxylase (TH)]-expressing, calretinin⁺ (CR), and calbindin⁺ (CB) amacrine cells and calbindin⁺ horizontal cells stratify within the correct retinal laminae. Glial fibrillary acidic protein (GFAP) immunostaining to visualize astrocytes is shown as a retina flat mount; all other retina images are transverse sections. The TH, neurofilament (NF), and DAPI images are from the central retina, where Cre expression is minimal. ONL outer nuclear layer, INL inner nuclear layer, GCL ganglion cell layer. Bars to the right of the cross-section images: upper bar (ONL), middle bar (INL), lower bar (GCL). N = 3 for each genotype. Scale bars, 100 μm. b Central projections of RGC axons in adult Pax6α-Cre;Rac1 ^CKO/− mice target the major retino-recipient areas as revealed by anterograde labeling by intraocular injection of cholera toxin subunit B. Major retino-recipient nuclei are indicated by arrows or a line for the LGN. LGN lateral geniculate nucleus, MTN medial terminal nucleus, OPN olivary pretectal nucleus, PA pretectal area, SC superior colliculus, SCN suprachiasmatic nucleus. N = 2 for each genotype. Scale bar, 1 mm. c Alkaline phosphatase (AP) histochemistry reveals the central projections of Cre-expressing RGC axons in adult Pax6α-Cre;Brn3b ^CKOAP/+ and Pax6α-Cre;Rac1 ^CKO/− ;Brn3b ^CKOAP/+ mice. Major retino-recipient nuclei are indicated by green and red arrows or a line for the LGN and labeled as in panel (b). N = 2 for each genotype. Scale bars, 1 mm