An alternative retinoid pathway regulating vertebrate neurogenesis

我们已经确定了一种新的方法来控制发育中的神经系统中的细胞是继续增殖还是停止分裂并成为神经细胞。我们的初步实验强烈表明，这是由一种名为脂肪酸结合蛋白5（Fabp 5）的基因的表达指导的;当Fabp 5在早期神经系统中过度表达时，细胞会不断分裂，而阻断其表达会减少细胞增殖。在皮肤细胞中，Fabp 5已被证明通过结合视黄酸并将其呈递给刺激增加细胞增殖和存活的基因的受体来促进细胞分裂。此外，Fabp 5的水平决定视黄酸是否促进或抑制增殖。我们建议在这里测试是否Fabp 5的作品在脊椎动物的神经组织和胚胎干细胞（ES）的类似机制。如果是这样的话，我们可能能够使用Fabp 5来协调和指导培养皿中的ES细胞分化，从而改善神经组织的产生，以用于神经损伤或疾病后的替代或用于测试新药的效果。抑制Fabp 5还可能增加用于治疗神经母细胞瘤（一种侵袭性儿童癌症）的视黄酸介导的分化疗法的有效性。

We have identified a novel way to control whether cells in the developing nervous system continue to multiply or stop dividing and become nerve cells. Our preliminary experiments strongly suggest that this is directed by the expression of a gene called fatty acid binding protein 5 (Fabp5); when Fabp5 is over-expressed in the early nervous system cells keep dividing, while blocking its expression reduces cell proliferation. In skin cells, Fabp5 has been shown to promote cell division by binding retinoic acid and presenting this to a receptor that stimulates genes that increase cell proliferation and survival. Furthermore, levels of Fabp5 determine whether retinoic acid promotes or inhibits proliferation. We propose here to test whether Fabp5 works by a similar mechanism in vertebrate neural tissue and in embryonic stem (ES) cells. If this is the case, we may be able to use Fabp5 to coordinate and direct ES cell differentiation in culture dishes and so improve the production of neural tissue for replacement following neural damage or disease or for testing the effects of new drugs. Inhibiting Fabp5 might also increase the effectiveness of retinoic acid mediated differentiation therapy used to treat Neuroblastoma, an aggressive childhood cancer.