Transforming growth factor-β is a survival factor for neonate cortical neurons: Coincident expression of type I receptors in developing cerebral cortices

Abstract

Transforming growth factor-β (TGF-β) 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-β in developing mice by in situ hybridization, revealing a significant difference in the expression of TGF-β type I and type II receptors. Unexpectedly, the TGF-β type I receptors were exclusively expressed without any detectable expression of the TGF-β type II receptors in developing cerebral cortices. In primary cortical neurons, a neutralizing antibody for TGF-β significantly reduced the expression of bcl-2 and subsequently induced neuronal cell death, indicating that TGF-β functions as a survival factor for cortical neurons in vitro. Consistent with the result of in situ hybridization, the TGF-β 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-β2 and the TGF-β type I receptors in developing cerebral cortices suggests that the TGF-β signaling system plays a pivotal role in neuronal differentiation and that unidentified components may be involved in TGF-β signaling in the development of the central nervous system.