An alternative retinoid pathway regulating vertebrate neurogenesis

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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.