The Abi/Wave complex is a novel regulator of TCR-mediated actin dynamics, IL-2 production, and proliferation.

Differential adhesion between migrating neurons and transient radial glial fibers enables the deployment of neurons into appropriate layers in the developing cerebral cortex. The identity of radial glial signals that regulate the termination of migration remains unclear. Here, we identified a radial glial surface antigen, SPARC (secreted protein acidic and rich in cysteine)-like 1, distributed predominantly in radial glial fibers passing through the upper strata of the cortical plate (CP) where neurons end their migration. Neuronal migration and adhesion assays indicate that SPARC-like 1 functions to terminate neuronal migration by reducing the adhesivity of neurons at the top of the CP. Cortical neurons fail to achieve appropriate positions in the absence of SPARC-like 1 function in vivo. Together, these data suggest that antiadhesive signaling via SPARC-like 1 on radial glial cell surfaces may enable neurons to recognize the end of migration in the developing cerebral cortex.

The cytoskeletal regulators that mediate the change in the neuronal cytoskeletal machinery from one that promotes oriented motility to one that facilitates differentiation at the appropriate locations in the developing neocortex remain unknown. We found that Nck-associated protein 1 (Nap1), an adaptor protein thought to modulate actin nucleation, is selectively expressed in the developing cortical plate, where neurons terminate their migration and initiate laminar-specific differentiation. Loss of Nap1 function disrupts neuronal differentiation. Premature expression of Nap1 in migrating neurons retards migration and promotes postmigratory differentiation. Nap1 gene mutation in mice leads to neural tube and neuronal differentiation defects. Disruption of Nap1 retards the ability to localize key actin cytoskeletal regulators such as WAVE1 to the protrusive edges where they are needed to elaborate process outgrowth. Thus, Nap1 plays an essential role in facilitating neuronal cytoskeletal changes underlying the postmigratory differentiation of cortical neurons, a critical step in functional wiring of the cortex.

Segmentation of the peripheral nervous system of vertebrates requires guidance cues located in the adjacent somitic mesoderm. Recent experiments suggest that inhibitory molecules in the posterior somite may influence segmentation by restricting the outgrowth of axons and the migration of neural crest cells to the anterior somite. A potential candidate for an inhibitory molecule is collagen IX, a chondroitin sulfate proteoglycan made by sclerotome cells of the somite and by the notochord. Immunohistochemical localization of collagen IX demonstrated that its expression in the posterior sclerotome of the somite correlates with axon outgrowth and neural crest cell migration through the anterior sclerotome. In vitro, sensory neurites on fibronectin, and motor neurites on basal lamina extract, avoid regions which contain substrate-bound collagen IX. This effect can be abolished by chondroitinase treatment, suggesting that the glycosaminoglycan component of the molecule is responsible for this activity. Further, collagen IX elicits a similar avoidance behavior by neural crest cells in vitro. These data suggest that collagen IX contributes to the segmentation of the peripheral nervous system in vivo.