Radial glia function during CNS development both as neural progenitors and as a scaffolding supporting neuronal migration. To elucidate pathways involved in these functions, we mapped in vivo the promoter for Blbp, a radial glial gene. We show here that a binding site for the Notch effector CBF1 is essential for all Blbp transcription in radial glia, and that BLBP expression is significantly reduced in the forebrains of mice lacking the Notch1 and Notch3 receptors. These results identify Blbp as the first predominantly CNS-specific Notch target gene and suggest that it mediates some aspects of Notch signaling in radial glia. Received February 2, 2005; revised version accepted March 25, 2005. During the development of the mammalian brain, billions of neurons have to be generated, sent to their appropriate locations, and then interconnected in a precise manner. This task is particularly complex in the cerebral cortex, where an inside-out mode of development results in newly generated neurons having to migrate over larger distances through increasingly crowded terrain as neurogenesis proceeds (Angevine and Sidman 1961). Numerous studies have documented the critical role played by the radial glial scaffold in facilitating this migration, and estimates are that as much as 90% of neuronal migration in the cortex may take place upon radial glial cells (Sidman and Rakic 1973;Hatten 1999). In addition to their structural role, radial glial cells also function as neuronal progenitors (Malatesta et al. 2000;Miyata et al. 2001;Noctor et al. 2001;Tamamaki et al. 2001) and have been shown to be the source of most neurons throughout the CNS (Anthony et al. 2004).The dual role played by radial glia as both migratory scaffolding and neuronal progenitors has suggested that there may be intimate links between the signaling pathways that control radial glial cell development, neuronal generation, and neuronal migration. The fact that migrating neurons regulate morphological and proliferative characteristics of glia (Hatten 1985) has led to considerable focus on neuronally derived signals, and several cell surface and diffusible molecules have been implicated in neuronal-radial glial signaling, including Astrotactin (Zheng et al. 1996), Neuregulin/ErbB2 (Anton et al. 1997;Rio et al. 1997;Patten et al. 2003;Schmid et al. 2003), and Notch (Gaiano et al. 2000;Gaiano and Fishell 2002;Patten et al. 2003;Schmid et al. 2003). In contrast, the genes expressed within radial glia that mediate the radial glial response to neuronal signaling are not well characterized. One candidate is brain lipid-binding protein (Blbp, Fabp7), a gene that is dynamically regulated in radial glia by migrating neurons (Feng et al. 1994;Kurtz et al. 1994;Feng and Heintz 1995). BLBP is a member of the large family of hydrophobic ligand-binding proteins (FABPs), molecules that have been shown to modulate transcription through their interactions with nuclear receptors and to play roles in metabolism (Haunerland and Spener 2004). Immunoelectron microscopy has demo...