SPARC-like 1 Regulates the Terminal Phase of Radial Glia-Guided Migration in the Cerebral Cortex

Differential adhesion between migrating neurons and tively, a change in the cell surface properties of the transient radial glial fibers enables the deployment radial glial substrate at the top of the cortical plate may of neurons into appropriate layers in the developing signal a migrating neuron to stop, detach, and differenti- cerebral cortex. The identity of radial glial signals that ate. To examine this hypothesis, we initiated studies to regulate the termination of migration remains unclear. identify and characterize cell surface cues specific to Here, we identified a radial glial surface antigen, radial glial cells that may be engaged in selective cell SPARC (secreted protein acidic and rich in cysteine)- recognition, adhesion, or translocation events neces- like 1, distributed predominantly in radial glial fibers sary to signal neurons to terminate their migration. passing through the upper strata of the cortical plate We identified a radial glial surface based molecule, (CP) where neurons end their migration. Neuronal mi- SPARC-like 1 (SC1), that is primarily localized in the gration and adhesion assays indicate that SPARC-like segment of radial glia spanning the upper cortical plate, 1 functions to terminate neuronal migration by reduc- where neurons terminate their migration. Inhibition of ing the adhesivity of neurons at the top of the CP. SPARC-like 1 in vivo perturbs the appropriate laminar Cortical neurons fail to achieve appropriate positions placement of cortical neurons. BrdU birthdating indi- in the absence of SPARC-like 1 function in vivo. To- cates neuronal misplacement in SC1 mutant mice. In gether, these data suggest that antiadhesive signaling vitro, SPARC-like 1 inhibits embryonic cortical neuron- via SPARC-like 1 on radial glial cell surfaces may en- glial adhesion. Ectopic expression of SPARC-like 1 in able neurons to recognize the end of migration in the vivo inhibits normal neuronal migration. The temporal developing cerebral cortex. and spatial distribution of SPRC-like 1 during cortical development in regions where neurons terminate their migration and its antiadhesive activity, both in vitro and