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Msx2 and p21(CIP1/WAF1) mediate the proapoptotic effects of bone morphogenetic protein-4 on ventricular zone

Nipan Israsena1, John A Kessler

  • 1Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.

Journal of Neuroscience Research
|September 3, 2002
PubMed

Insights

Bone morphogenetic protein-4 (BMP4) induces progenitor cell death via msx2 and p21. This proapoptotic effect diminishes as cells mature, with BMP4 no longer causing death in later developmental stages.

Area of Science:

  • Developmental biology
  • Cell biology
  • Neuroscience

Background:

  • Bone morphogenetic protein-4 (BMP4) is a signaling molecule with diverse roles in development.
  • Ventricular zone (VZ) progenitor cells are crucial for central nervous system development.
  • Understanding BMP4's role in progenitor cell fate is essential for developmental studies.

Purpose of the Study:

  • To investigate the role of BMP4 in VZ progenitor cell apoptosis.
  • To identify the molecular mechanisms underlying BMP4-induced apoptosis.
  • To determine how progenitor cell sensitivity to BMP4 changes during development.

Main Methods:

  • Primary cell culture of VZ progenitor cells at different embryonic days (E10-E18).
  • Treatment with varying doses of BMP4.
  • Gene expression analysis (msx2, p21, bax).
  • Apoptosis assays.
  • Gene inhibition and knockout studies.

Main Results:

  • BMP4 treatment induced dose-dependent apoptosis in early-stage VZ progenitor cells.
  • Progenitor cells became resistant to BMP4-induced apoptosis with increasing developmental age (E10-E18).
  • BMP4-mediated apoptosis required msx2 and p21 expression; inhibiting either gene blocked apoptosis.
  • Knockout of bax partially reduced BMP4-induced cell death, indicating a partial role for this apoptotic regulator.

Conclusions:

  • Msx2 and p21 are key mediators of BMP4-induced apoptosis in VZ progenitor cells.
  • Both msx2 and p21 are necessary but not sufficient to induce apoptosis independently.
  • BMP4's apoptotic function on progenitor cells is developmentally regulated, decreasing with maturation.

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