Migrating neurons move along tracks laid by radial glia. In the cerebellum, radial (Bergmann) glia arise from cerebellar astroglia, a process triggered by glialneuronal contact. This glial differentiation involves activation of Notch1 and binding of its intracellular domain to Suppressor of Hairless [Su(H)] and Deltex1 (DTX1). These canonical and noncanonical pathways lead to expression of brain lipid binding protein (BLBP) and the receptor tyrosine kinase erbB2, respectively. BLBP affects cellcell adhesion, whereas glial erbB2 interacts with neuregulin I expressed by migrating granule cells. This week, Patten et al. report that overexpression of DTX1 or a dominant-negative form disrupted Su(H)-mediated signaling, but expression of Su(H) had no effect on DTX1-induced events. In contrast, RNAi-mediated knock-down of DTX1 selectively blocked the effects of DTX1, leaving Su(H) signaling intact. The authors propose a hierarchical relationship between the two pathways, in which radial glia differentiation depends on the relative expression of the two molecules.
2. Motoneuron Differentiation from ES Cells
Prabakaran Soundararajan, Gareth B. Miles, Lee L. Rubin, Robert M. Brownstone, and Victor F. Rafuse
This week, Soundararajan et al. provide additional evidence that embryonic stem (ES) cells can be directed to generate defined classes of motoneurons, an important general issue for successful cell transplantation. The authors treated ES cells with sonic hedgehog (Shh) ligand and retinoic acid (RA) for 5 d in culture and tracked the cells with enhanced green fluorescent protein (eGFP) under control of the Hb9 promoter. Most of the Hb9-expressing motoneurons also expressed Lhx3 in vitro, a homeobox gene that distinguishes motoneurons in the medial aspect of the medial motor column (MMCm)
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