Tomoda T, Shirasawa T, Yahagi Y I, Ishii K, Takagi H, Furiya Y, Arai K I, Mori H, Muramatsu M A
Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Japan.
Dev Biol. 1996 Oct 10;179(1):79-90. doi: 10.1006/dbio.1996.0242.
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.
转化生长因子-β（TGF-β）是一种多功能多肽，在细胞增殖、分化和器官形成的调节中起着关键作用。在本研究中，我们通过原位杂交研究了发育中小鼠体内TGF-β信号受体的表达，发现TGF-βⅠ型和Ⅱ型受体的表达存在显著差异。出乎意料的是，在发育中的大脑皮层中，TGF-βⅠ型受体单独表达，而未检测到TGF-βⅡ型受体的表达。在原代皮层神经元中，TGF-β的中和抗体显著降低了bcl-2的表达，随后诱导神经元细胞死亡，表明TGF-β在体外作为皮层神经元的存活因子发挥作用。与原位杂交结果一致，通过亲和交联和RT-PCR分析在原代皮层神经元中检测到了TGF-βⅠ型受体而非Ⅱ型受体。发育中的大脑皮层中TGF-β2和TGF-βⅠ型受体的共同表达表明，TGF-β信号系统在神经元分化中起关键作用，并且在中枢神经系统发育过程中，可能有未鉴定的成分参与TGF-β信号传导。
