Transforming growth factor-beta is a survival factor for neonate cortical neurons: coincident expression of type I receptors in developing cerebral cortices.
Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide which plays a crucial role in the regulation of cell proliferation, differentiation, and organogenesis. In the present study, we investigated the expression of signaling receptors for TGF-beta in developing mice by in situ hybridization, revealing a significant difference in the expression of TGF-beta type I and type II receptors. Unexpectedly, the TGF-beta type I receptors were exclusively expressed without any detectable expression of the TGF-beta type II receptors in developing cerebral cortices. In primary cortical neurons, a neutralizing antibody for TGF-beta significantly reduced the expression of bcl-2 and subsequently induced neuronal cell death, indicating that TGF-beta functions as a survival factor for cortical neurons in vitro. Consistent with the result of in situ hybridization, the TGF-beta, type I but not type II receptors were detected in primary cortical neurons by affinity crosslink and RT-PCR analyses. The concomitant expression of TGF-beta2 and the TGF-beta type I receptors in developing cerebral cortices suggests that the TGF-beta signaling system plays a pivotal role in neuronal differentiation and that unidentified components may be involved in TGF-beta signaling in the development of the central nervous system.
Tomoda
T
T
Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Japan.
Shirasawa
T
T
Yahagi
Y I
YI
Ishii
K
K
Takagi
H
H
Furiya
Y
Y
Arai
K I
KI
Mori
H
H
Muramatsu
M A
MA
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D002454:Cell Differentiation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology* / Q000254:growth & development*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta