A novel role for the choroid plexus in BMP-mediated inhibition of differentiation of cerebellar neural progenitors.
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.
Krizhanovsky
Valery
V
Department of Cell and Animal Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Ben-Arie
Nissim
N
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002831:Choroid Plexus / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018797:Cell Cycle Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; C500943:Atoh1 protein, mouse; C490089:Nbl1 protein, mouse