The effects of bone morphogenetic protein 2 and 4 (BMP2 and BMP4) on gap junctions during neurodevelopment.
Nervous system deficits account for the third largest group of fatal birth defects (after heart and respiratory problems) in North America. Although considerable advance has been made in neuroscience research, the early events involved in neurogenesis remain to be elucidated. More specifically, the effects of signaling molecules on intercellular communication during neurodevelopment have not yet been studied. The development of the central nervous system is regulated, at least in part, by signaling molecules such as bone morphogenetic proteins (BMPs). In this study, we have used the embryonal mouse P19 cell line to examine the effects of BMP2 and BMP4 on gap junctional communication as well as neuronal and astrocytic differentiation. The undifferentiated P19 cells show high levels of the gap junction protein, connexin43 (Cx43), and functional intercellular coupling. However, Cx43 expression and dye coupling decrease as these cells differentiate into neurons and astrocytes. In contrast, cells treated with BMP2 or BMP4 lose their capacity to differentiate into neurons but not astrocytes, while they maintain extensive gap junctional communication. The very few neurons that remain in the BMP-treated cultures are coupled (a characteristic not seen in the control neurons). Together, our data suggest that BMPs may play a critical role in morphogenesis of P19 cells while they affect gap junctions.
Bani-Yaghoub
M
M
Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Felker
J M
JM
Sans
C
C
Naus
C C
CC
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D015152:Blotting, Northern; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000737:chemistry / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D014411:Neoplastic Stem Cells; D009420:Nervous System / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018031:Connexin 43; D005452:Fluoresceins; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C085925:calcein AM