Stem cells

Direct isolation of human central nervous system stem cells. Uchida, N. et al. Proc. Natl Acad. Sci. USA 97, 14720–14725 (2000)

Until recently, isolation of human neural stem cells required prior transfection of the tissue with the green fluorescent protein gene driven by the nestin promoter. Uchida et al. identified a set of antibodies that enables sorting on the basis of surface marker expression. Using 5F3, which detects the CD133 antigen, and the novel antibody 5E12 raised against fetal brain, they isolated stem cells directly from fresh brain tissue. This method for isolating human stem cells bypasses the need for genetic manipulation.

Neuropathology

Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Brenner, M. et al. Nature Genet. 27, 117–120 (2001)

Alexander disease is a rare brain disorder that is characterized by macrocephaly and seizures, and by the appearance of cytoplasmic inclusions in astrocytes. These inclusions contain glial fibrillary acidic protein (GFAP), indicating that defects in the GFAP gene may be the causative factor. This was confirmed by Brenner et al., who showed that patients with different variants of the disease all had mutations in GFAP. This is the first genetic brain disorder that has been attributed to a defect in astrocytes.

Computational Neuroscience

A global geometric framework for nonlinear dimensionality reduction. Tenenbaum, J. B. et al. Science 290, 2319–2323 (2000)

How does the brain extract a few perceptually relevant features from the high-dimensional sensory stimuli that it receives? This and another paper in the same issue of Science used a mathematical approach to address this problem known as dimensionality reduction. The algorithms developed in both papers obtained accurate solutions using artificial and real data. As dimensionality reduction is a problem encountered in many branches of science, these algorithms are likely to have widespread application.

Development

LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome. Feng, Y. et al. Neuron 28, 665–679 (2000)

Mutations in LIS1 cause lissencephaly, a developmental disorder related to defects in neuronal migration. The precise relationship between LIS1 and cell migration is not known, but recent work has indicated that it may involve LIS1 interaction with centrosome proteins. This and two related papers in the same issue of Neuron provide additional evidence for this hypothesis by showing that LIS1 binds to newly identified centrosome proteins that have homologues in the fungus Aspergillus nidulans.