アクティブボード・2014年 5月
     ・・・・・2014年 5月 1日更新・・・・・

研究発表を行った学会;
・The 18th International Vascular Biology Meeting
 2014年4月14日〜17日(京都)
タイトル;Tsukushi maintains the growth and undifferentiated properties of neuronal stem/progenitor cells.
発表者;太田 訓正 氏
   (熊本大学 大学院生命科学研究部 神経分化学分野)
Abstract;
We have been studying the molecular function of Tsukushi (TSK), which is a soluble molecule containing 12 leucine-rich repeats and belongs to the Small Leucine-Rich Proteoglycan family. TSK functions as a multiple signaling modulator at the extracellular region by regulating TGF-β, FGF, Notch, and Wnt signaling cascades. We have generated KO mice lacking TSK function and found that TSK inactivation results in expansion of the adult ciliary body and the increased proliferation of the retinal stem/progenitor cells in vitro. Biochemical assays and overexpression experiments in the retina suggested that these effects are dependent on the ability of TSK to modulate Wnt signaling by direct binding to Fzd 4 receptor.
In the adult mouse brain, TSK is strongly expressed in the Subventricular Zone and Dentate Gyrus, where brain stem cells are located. Interestingly, TSK KO mouse showed the enlargement of Lateral Ventricule (LV). By immunochistochemical study, we found that TSK is expressed in the ependymal cell layer. BrdU labelling study showed that the number of BrdU-positive S phase cells is increased in TSK KO mouse brain. We observed the abnormal blood vessel formation along the LV and the enhanced the cell migration with aorta ring assay in TSK KO mouse. Taken together, we uncover a new crucial role for TSK in maintaining the growth and undifferentiated properties of neuronal stem/progenitor cells as a niche molecule.