THE CELL-CYCLE GENE SKP1 IS REGULATED BY LIGHT IN POSTNATAL RAT-BRAIN

During the early postnatal phase of high neuronal plasticity, an alter ed visual input leads to great modifications of visual cortex organiza tion [Y. Fregnac, M. Imbert, Development of neuronal selectivity in pr imary visual cortex of cat, Physiol. Rev., 64 (1984) 375-434; D.H. Hub el, T.N. Wiesel, S. LeVay, Plasticity of ocular dominance columns in m onkey striate cortex, Philos. Trans. R. Sec. London, Ser. B, 278 (1977 ) 377-409.]. We used refined differential screening of an organized cD NA library to identify the genes that may participate in this plastici ty. We isolated a candidate plasticity gene encoding for a 163 aa prot ein that is closely related to the human and yeast Skplp, a key factor in cell cycle progression [C. Bai, K. Hofman, L. Ma, M. Goebl, J.W. H arper, S.J. Elledge, SKP1 connects cell cycle regulators to the ubiqui tin proteolysis machinery through a novel motif, the F-box, Cell, 86 ( 1996) 263-274; C. Connelly, P. Hieter, Budding yeast SKP1 encodes an e volutionary conserved kinetochore protein required for cell cycle prog ression, Cell, 86 (1996) 275-285; H. Zhang, R. Kobayashi, K. Galaktion ov, D. Beach, p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase, Cell, 82 (1995) 915-925.]. Northern blot analy sis showed that the expression of SKP1 (Skplp gene) dramatically decre ased after 2 h of light stimulation in the visual cortex of young dark -reared rats. This down regulation lasted at least 72 h. It was specif ic for the critical period as we did not observe any significant regul ation of SKP1 mRNA by light in adult dark-reared rat brain. The down r egulation was observed in the superior colliculus but also in the fron tal cortex and in the hippocampus. The fact that this down regulation was not restricted to the visual system, suggested that it could be pr oduced by dark rearing-induced hormonal changes. The significance of S KP1 expression in the brain and its regulation are discussed. (C) 1998 Elsevier Science B.V.