研究発表を行った学会；第２８回日本分子生物学会年会
２００５年１２月　７日〜１２月１０日（福岡）
タイトル；シグナル伝達分子SOCS3によるアストロサイトの分化制御機構
発表者；福田　信治　氏
　　　（熊本大学　発生医学研究センター　転写制御分野）
Abstract；
Mammalian central nervous system mainly consists of neurons, astrocytes and oligodendrocytes; all of which arise from common progenitor cells. Leukemia inhibitory factor (LIF) and bone morphogenetic protein 2 (BMP2) act on neural progenitor cells to induce astrocytes. Upon binding of LIF and BMP2 to their respective receptors, downstream transcription factors, STAT3 and Smad1, cooperatively initiate the expression of genes for molecules such as glial fibrillary acidic protein (GFAP). However, it remains unclear how the sensitivity of such signaling pathways is regulated. Here, we show that a negative feedback regulator, suppressor of cytokine signaling 3 (SOCS3), is induced in neuroepithelial cells in response to LIF. Overexpression of SOCS3 causes neuroepithelial cells to resist LIF-induced astrocytic differentiation by suppressing the activation of STAT3. Conversely, SOCS3-deficient neuroepithelial cells readily differentiate into astrocytes by LIF. This effect is not only due to the sustained activation of STAT3 by exogenously added LIF but also due to the unexpected transient activation of Smad1 by endogenously produced BMP2. When compared to their wild-type littermates, SOCS3-deficient mice exhibit the increased number of astrocytes in the neonatal brain and the enhanced activation of STAT3 in the adult spinal cord after injury. Our study suggests that astrocytogenesis is controlled by the multiple feedback regulation of cytokine signaling.