Developmental changes in progenitor cell responsiveness to gone morphogenetic; Proteins differentially modulate progressive CNS lineage fate

Mark F. Mehler, Peter C. Mabie, Gaofa Zhu, Solen Gokhan, John A. Kessler

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168 Citations (Scopus)

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. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalDevelopmental Neuroscience
Volume22
Issue number1-2
StatePublished - Feb 2000

Fingerprint

Bone Morphogenetic Proteins
Stem Cells
Proteins
Oligodendroglia
Cell Death
Astrocytes
Neurons
Brain

Keywords

  • Apoptosis
  • Bone morphogenetic proteins
  • Cellular responsiveness
  • Cerebral cortex
  • Developmental context
  • Gliogenesis
  • Neurogenesis
  • Progenitor cells
  • Subventricular zone
  • Ventricular zone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Developmental changes in progenitor cell responsiveness to gone 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. Copyright (C) 2000 S. Karger AG, Basel.",
keywords = "Apoptosis, Bone morphogenetic proteins, Cellular responsiveness, Cerebral cortex, Developmental context, Gliogenesis, Neurogenesis, Progenitor cells, Subventricular zone, Ventricular zone",
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T1 - Developmental changes in progenitor cell responsiveness to gone morphogenetic; Proteins differentially modulate progressive CNS lineage fate

AU - Mehler, Mark F.

AU - Mabie, Peter C.

AU - Zhu, Gaofa

AU - Gokhan, Solen

AU - Kessler, John A.

PY - 2000/2

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N2 - 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. Copyright (C) 2000 S. Karger AG, Basel.

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KW - Apoptosis

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KW - Developmental context

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