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 c onsiderable advance has been made in neuroscience research, the early event s involved in neurogenesis remain to be elucidated. More specifically, the effects of signaling molecules on intercellular communication during neurod evelopment have not yet been studied. The development of the central nervou s system is regulated, at least in part, by signaling molecules such as bon e morphogenetic proteins (BMPs). In this study we have used the embryonal m ouse P19 cell line to examine the effects of BMP2 and BMP4 on gap junctiona l communication as well, as neuronal and astrocytic differentiation. The un differentiated P19 cells show high levels of the gap junction protein, conn exin43 (Cx43), and functional intercellular coupling. However, Cx43 express ion and dye coupling decrease as these cells differentiate into neurons and astrocytes. In contrast, cells treated with BMP2 or BMP4 lose their capaci ty to differentiate into neurons but not astrocytes, while they maintain ex tensive gap junctional communication. The very few neurons that remain in t he BMP-treated cultures are coupled (a characteristic not seen in the contr ol neurons). Together, our data suggest that BMPs may play a critical Pole in morphogenesis of P19 cells while they affect gap junctions. (C) 2000 Aca demic Press.