Journal
DEVELOPMENTAL NEUROSCIENCE
Volume 22, Issue 1-2, Pages 74-85Publisher
KARGER
DOI: 10.1159/000017429
Keywords
bone morphogenetic proteins; neurogenesis; gliogenesis; apoptosis; cerebral cortex; cellular responsiveness; progenitor cells; developmental context; ventricular zone; subventricular zone
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Funding
- NIMH NIH HHS [R01 MH066290] Funding Source: Medline
- NINDS NIH HHS [NS35320, NS20013, NS38902] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH066290] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038902, R01NS035320, R01NS020013] Funding Source: NIH RePORTER
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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 develop mental 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. Copyright (C) 2000 S. Karger AG, Basel.
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