title: Developmental changes in progenitor cell responsiveness to bone morphogenetic proteins differentially modulate progressive CNS lineage fate.
abstract: Although multipotent progenitor cells capable of generating neurons, astrocytes and oligodendrocytes are present within the germinal zones of the brain throughout embryonic, postnatal and adult life, the different neural cell types are generated within discrete temporospatial developmental windows. This might suggest that multipotent progenitor cells encounter different signals during each developmental stage, thus accounting for separate waves of lineage commitment and cellular differentiation. This study demonstrates, however, that progenitor cell responses to the same class of signals, the bone morphogenetic proteins (BMPs), change during ontogeny, and that these same signals may thus initiate progenitor cell elaboration of several different lineages. BMPs promote cell death and inhibit the proliferation of early (embryonic day 13, E13) ventricular zone progenitor cells. At later embryonic (E16) stages of cerebral cortical development, BMPs exhibit a concentration-dependent dissociation of cellular actions, with either enhancement of neuronal and astroglial elaboration (at 1-10 ng/ml) or potentiation of cell death (at 100 ng/ml). Finally, during the period of perinatal cortical gliogenesis, BMPs enhance astroglial lineage elaboration. By contrast, oligodendroglial lineage elaboration is inhibited by the BMPs at all stages. Further, application of the BMP antagonist noggin to cultured progenitors promotes the generation of oligodendrocytes, indicating that endogenous BMP signaling can actively suppress oligodendrogliogenesis. These observations suggest that developmental changes in neural progenitor cell responsiveness to the BMPs may represent a novel mechanism for orchestrating context-specific cellular events such as lineage elaboration and cellular viability.
authors.affiliation: Department of Neurology, the Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, N.Y., USA. mehler@aecom.yu.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Mehler
authors.forename: P C
authors.initials: PC
authors.lastname: Mabie
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Gokhan
authors.forename: J A
authors.initials: JA
authors.lastname: Kessler
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D005314:Embryonic and Fetal Development / Q000502:physiology; D006801:Humans; D009836:Oligodendroglia / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta