title: BM88 is an early marker of proliferating precursor cells that will differentiate into the neuronal lineage.
abstract: Progression of progenitor cells towards neuronal differentiation is tightly linked with cell cycle control and the switch from proliferative to neuron-generating divisions. We have previously shown that the neuronal protein BM88 drives neuroblastoma cells towards exit from the cell cycle and differentiation into a neuronal phenotype in vitro. Here, we explored the role of BM88 during neuronal birth, cell cycle exit and the initiation of differentiation in vivo. By double- and triple-labelling with the S-phase marker BrdU or the late G2 and M-phase marker cyclin B1, antibodies to BM88 and markers of the neuronal or glial cell lineages, we demonstrate that in the rodent forebrain, BM88 is expressed in multipotential progenitor cells before terminal mitosis and in their neuronal progeny during the neurogenic interval, as well as in the adult. Further, we defined at E16 a cohort of proliferative progenitors that exit S phase in synchrony, and by following their fate for 24 h we show that BM88 is associated with the dynamics of neuron-generating divisions. Expression of BM88 was also evident in cycling cortical radial glial cells, which constitute the main neurogenic population in the cerebral cortex. In agreement, BM88 expression was markedly reduced and restricted to a smaller percentage of cells in the cerebral cortex of the Small eye mutant mice, which lack functional Pax6 and exhibit severe neurogenesis defects. Our data show an interesting correlation between BM88 expression and the progression of progenitor cells towards neuronal differentiation during the neurogenic interval.
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, Athens 115 21, Greece.
authors.forename: Yassemi
authors.initials: Y
authors.lastname: Koutmani
authors.forename: Catherine
authors.initials: C
authors.lastname: Hurel
authors.forename: Evangelia
authors.initials: E
authors.lastname: Patsavoudi
authors.forename: Michael
authors.initials: M
authors.lastname: Hack
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gotz
authors.forename: Dimitra
authors.initials: D
authors.lastname: Thomaidou
authors.forename: Rebecca
authors.initials: R
authors.lastname: Matsas
mesh_terms: D000367:Age Factors; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D049109:Cell Proliferation; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004622:Embryo, Mammalian; D005136:Eye Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D016571:Neural Networks, Computer; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013936:Thymidine / Q000493:pharmacokinetics; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D027322:Amino Acid Transport System X-AG; D000941:Antigens; D015415:Biomarkers; D001973:Bromodeoxyuridine; D002232:Carbocyanines; D019926:Cyclin B; D056744:Cyclin B1; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010751:Phosphopyruvate Hydratase; D011509:Proteoglycans; D012333:RNA, Messenger; D012097:Repressor Proteins; D012794:Sialic Acids; D013936:Thymidine; D014316:Tritium; D000099216:Chondroitin Sulfate Proteoglycan 4; C035005:3,3'-dihexadecylindocarbocyanine; C534700:Ccnb1 protein, mouse; C534701:Ccnb1 protein, rat; C496858:Cend1 protein, mouse; C496857:Cend1 protein, rat; C577485:Nes protein, mouse; C577486:Nes protein, rat; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; C103469:polysialyl neural cell adhesion molecule