Msx2 and p21(CIP1/WAF1) mediate the proapoptotic effects of bone morphogenetic protein-4 on ventricular zone progenitor cells.
Treatment of cultured ventricular zone (VZ) progenitor cells with bone morphogenetic protein-4 (BMP4) promoted cell death in a dose-dependent manner. VZ progenitor cells became progressively more resistant to the proapoptotic effects of BMP4 between E10 and E16, and, by E18 and thereafter, BMP4 treatment no longer led to progenitor cell death. BMP4 treatment of E13 progenitor cells promoted expression of msx2 and p21(CIP1/WAF1) (p21) and inhibition of expression of either gene prevented BMP4-mediated apoptosis. Treatment of E18 cells with BMP4 failed to induce apoptosis but still induced expression of low levels of msx2 and p21. Knockout of bax significantly reduced but did not prevent BMP4-mediated death of E13 murine progenitor cells. These observations indicate that msx2 and p21 mediate the proapoptotic effects of BMP4 on VZ progenitor cells and that each gene is necessary but insufficient to promote apoptosis.
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
Nipan
N
Israsena
John A
JA
Kessler
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000502:physiology; D018398:Homeodomain Proteins; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein