The Effects of Bone Morphogenetic Protein 2 and 4 (BMP2 and BMP4) on Gap Junctions during Neurodevelopment

• Published in: Experimental neurology Vol. 162; no. 1; pp. 13 - 26
• Main Authors: Bani-Yaghoub, Mahmud, Felker, Josh M., Sans, Christopher, Naus, Christian C.G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2000
• Subjects: Animals; Astrocytes - chemistry; Astrocytes - cytology; Astrocytes - physiology; Blotting, Northern; BMP; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins - genetics; Cell Communication - physiology; Cell Differentiation - physiology; Cell Division - physiology; connexin; Connexin 43 - genetics; dye coupling; Fluoresceins; Fluorescent Dyes; Gap Junctions - chemistry; Gap Junctions - physiology; Gene Expression Regulation, Developmental - physiology; intercellular communication; Mice; Neoplastic Stem Cells; Nervous System - cytology; Nervous System - embryology; neuronal differentiation; Neurons - chemistry; Neurons - cytology; Neurons - physiology; P19; RNA, Messenger - analysis; Transcription, Genetic - physiology; Transforming Growth Factor beta; Tumor Cells, Cultured; intercellular communication; P19; BMP; dye coupling; connexin; neuronal differentiation
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7294

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.