Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype

Peter C. Mabie, Mark F. Mehler, John A. Kessler

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Members of the bone morphogenetic protein (BMP) family have been implicated in multiple aspects of neural development in both the CNS and peripheral nervous system. BMP ligands and receptors, as well as the BMP antagonist noggin, are expressed in the developing cerebral cortex, making the BMPs likely candidates for regulating cortical development. To define the role of these factors in the developing cerebral cortex, we examined the effects of BMP2 and BMP4 on cortical cells in vitro. Cells were cultured from embryonic day 13 (E13) and E16 rat cerebral cortex in the absence or presence of different concentrations of fibroblast growth factor 2, a known regulator of cortical cell proliferation and differentiation. At E13, the BMPs promoted cell death and inhibited proliferation of cortical ventricular zone cells, resulting in the generation of fewer neurons and no glia. At E16, the effects of the BMPs were more complex. Concentrations of BMP2 in the range of 1-10 ng/ml promoted neuronal and astroglial differentiation and inhibited oligodendroglial differentiation, whereas 100 ng/ml BMP2 promoted cell death and inhibited proliferation. Addition of the BMP antagonist noggin promoted oligodendrogliogenesis in vitro, demonstrating that endogenous BMP signaling influences the differentiation of cortical cells in vitro. The distribution of BMP2 and noggin within the developing cortex suggests that local concentrations of ligands and antagonists define gradients of BMP signaling during corticogenesis. Together, these results support the hypothesis that the BMPs and their antagonist noggin co-regulate cortical cell fate and morphogenesis.

Original languageEnglish (US)
Pages (from-to)7077-7088
Number of pages12
JournalJournal of Neuroscience
Volume19
Issue number16
StatePublished - Aug 15 1999

Fingerprint

Bone Morphogenetic Proteins
Cell Count
Phenotype
Cerebral Cortex
Cell Differentiation
Cell Death
Bone Morphogenetic Protein Receptors
Ligands
Peripheral Nervous System
Fibroblast Growth Factor 2
Morphogenesis
Neuroglia
Cultured Cells
Cell Proliferation
Neurons
In Vitro Techniques

Keywords

  • Bone morphogenetic protein
  • Embryogenesis
  • Fibroblast growth factor
  • Gliogenesis
  • Neurogenesis
  • Noggin
  • Subventricular zone
  • Ventricular zone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype. / Mabie, Peter C.; Mehler, Mark F.; Kessler, John A.

In: Journal of Neuroscience, Vol. 19, No. 16, 15.08.1999, p. 7077-7088.

Research output: Contribution to journalArticle

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