Cerebellar granule cells, the most abundant neurons in the mammalian brain, arise in the rhombic lip located at the roof of the brain's fourth ventricle. Bordering the rhombic lip is the choroid plexus, a non-neuronal structure, composed of blood vessels enveloped by epithelial cells. Here, we show a striking decrease in neural differentiation of rhombic lip-derived cells, which failed to extend neuritic processes and attenuate Math1 promoter activity, when co-cultured with choroid plexus cells. Moreover, a blocking antibody against BMP7, a morphogenetic protein expressed in the choroid plexus, blocked the inhibitory effect of the choroid plexus, whereas purified BMP7 mimicked this effect, demonstrating causal involvement of BMP. On the other hand, the BMP antagonist NBL1 promoted neurogenesis in rhombic lip cultures from Math1 null mice displaying arrested differentiation. Our data indicate that besides its secretory and barrier functions, the choroid plexus has a novel role in attenuating the differentiation of adjacent neural progenitors.
Bibliographical noteFunding Information:
We thank Tamar Golan-Lev, Theodora Bar-El and Esther Golenser for their valuable assistance. We gratefully acknowledge Huda Y. Zoghbi (Houston, TX) for providing us with Math1 knockout mice. We thank Hermona Soreq, Marshall Devor, Uri Gat and Allan Bar-Sinai for careful reading of the manuscript and suggestions. This work was supported by grants from the Israel Science Foundation (587/02), US-Israel Binational Science Foundation (1998-066) and the European Community (QLG3-CT-2000-00072). N.B.A is a member of the Roland Center for Neurodegenerative Diseases and the Otto Loewi Minerva Center for Cellular and Molecular Neurobiology, The Hebrew University of Jerusalem.
- Cerebellar granule cells
- Choroid plexus
- Rhombic lip