X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin. Four double cortex/X-linked lissencephaly families and three sporadic double cortex patients show independent doublecortin mutations, at least one of them a de novo mutation. Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin does not contain a kinase domain, it is homologous to the amino terminus of a predicted kinase protein, indicating a likely role in signal transduction. Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration.

Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin 1 (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis.

Biodiversity-ecosystem functioning experiments have established that species richness and composition are both important determinants of ecosystem function in an experimental context. Determining whether this result holds for real-world ecosystem services has remained elusive, however, largely due to the lack of analytical methods appropriate for large-scale, associational data. Here, we use a novel analytical approach, the Price equation, to partition the contribution to ecosystem services made by species richness, composition and abundance in four large-scale data sets on crop pollination by native bees. We found that abundance fluctuations of dominant species drove ecosystem service delivery, whereas richness changes were relatively unimportant because they primarily involved rare species that contributed little to function. Thus, the mechanism behind our results was the skewed species-abundance distribution. Our finding that a few common species, not species richness, drive ecosystem service delivery could have broad generality given the ubiquity of skewed species-abundance distributions in nature.