title: Differentiation of postnatal cerebellar glial progenitors is controlled by Bmi1 through BMP pathway inhibition.
abstract: Bmi1 is a polycomb group (Pc-G) protein involved in heritable gene repression, maintenance of cell identity, and proliferation. During the development of the central nervous system, Bmi1 is crucial for self-renewal of neural stem cells and for proliferation of neuronal (granule cell) progenitors of the cerebellum. Here, we use loss of function mouse models and in vitro assays--granule cell cultures and glial-neuronal co-cultures--to show that Bmi1 plays a crucial role in specification of glial progenitors during postnatal cerebellar development. Moreover, we demonstrate in in vitro assays that Bmi1 exerts this novel function through repression of BMP pathway and that this is independent of its known role in mediating the cellular response to Shh signaling. Thus modulation of Bmi1 expression in glial progenitors may represent a key event in determining the differentiation potential of these cells.
authors.affiliation: Blizard Institute of Cell and Molecular Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, United Kingdom.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Antonella
authors.initials: A
authors.lastname: Santuccione
authors.forename: Carly
authors.initials: C
authors.lastname: Leung
authors.forename: Silvia
authors.initials: S
authors.lastname: Marino
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D018920:Coculture Techniques / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D011509:Proteoglycans / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009687:Nuclear Proteins; D063150:Polycomb Repressive Complex 1; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C500943:Atoh1 protein, mouse; C489421:Bmi1 protein, mouse; C546888:Shh protein, rat