Neural progenitors find VEGF attractive

Cells need backward motor to move forward ytoplasmic dynein associates with a variety of intracellular cargos and pulls them toward the minus ends of microubules. But this retrograde motor protein is also essential for forward cell migration, as Dujardin et al. demonstrate on page 1205. After observing dynein and its associated regulatory proteins at the leading edges of migrating cells in a monolayer model of wound healing, the authors inhibited dynein activity at various times to identify its functions. Early in cell migration, dynein helps reorganize the microtubule cytoskeleton, placing the centro-some on the leading edge side of the nucleus. Once this rearrangement is completed, inhibiting dynein does not change the location of the centrosome. The motor protein is still required for cell migration even after cytoskeletal rearrangement. During migration, dynein appears in a diffuse area along the leading edge of the cell, where it seems to capture the plus ends of microtubules that enter the region. It is unclear whether dynein at the leading edge is activating lamellipodial protrusion or serving a strictly mechanical function, but the mechanism might have parallels with the action of dynein at the kinetochore, where it both pulls on micro-tubules and participates in mitotic checkpoint signaling. ᭿ C Dynein (green) at the front of the cell helps the cell move. lood vessels and neural stem cells can be led to their targets by the same factor, say Zhang et al. on page 1375. The factor, vascular endothelial growth factor A (VEGF), is known as a major inducer of angio-genesis. Zhang et al. show that it is also a powerful attractant for immature neural progenitor cells. In the developing mammalian brain, it may be used when both neural stem cell migration and blood vessel growth must head for the same brain region. The authors purified neural progenitors from the subventricular zones of newborn rats, and cultured them in the presence of fibroblast growth factor 2 (FGF-2) to prevent them from differentiating. The progenitor cells migrate up gradients of VEGF, in a chemotactic response specifically mediated by VEGF receptor 2. In cocultures in three-dimensional collagen matrices, the progenitors migrate toward VEGF-secreting cells. Progenitor cells that are allowed to differentiate into neuron-or glia-restricted lineages become insensitive to VEGF. The data suggest that VEGF links angiogene-sis to neurogenesis to establish neurogenic niches within the developing brain. Once the niches are established by immature progenitors , they could act …