Functions of c-Jun N-terminal Kinase (JNK) during neural development

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Mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) are involved in the intracellular pathways that respond to various extracellular signals. To compare the different contribution of these two kinases, JNK and ERK, during the neural development, we studied the differences in the in vivo distribution of their active forms. In the spinal cord of chick embryos, phosphorylated ERK (p-ERK) positive cells appeared in the ventral ventricular zone on embryonic day 4 (E4). From E6 onward, they appeared in the gray matter and were then localized abundantly in the white matter. A double labeling method revealed that these p-ERK positive cells included oligodendrocyte precursors. In the dorsal horn, p-ERK positive small cells appeared on E6. Subsequently, the positive cells in the dorsal horn increased transiently in numberand then decreased markedly by E10. Motoneurons also expressed p-ERK transiently on E7. In contrast … More , the expression of p-JNK was observed in early-projecting axons on E3. Subsequently, on E5 and E8, the expression of p-JNK increased in the axonal tracts in the spinal white matter. By E13, the expression of p-JNK was decreased in axons in the white matter, whereas strong p-JNK expression appeared in cell nuclei in the gray matter. These data showed the different distribution of these two kinases.We also studied the involvement of MAP kinase in the sex steroids-induced changes in the neural development, using primary cultures of developing hypothalamic cells. Estradiol-17beta (E2) did not increase activity of JNK but ERK. E2 also changed the distribution of synapsin l-immunoreactivity and significantly increased the area of synapsin l-immunoreactive puncta (synapsin l-puncta). E2 antagonist ICI182.780, actinomycin D (AMD) and cychoheximde (CHX) did not suppress the E2-induced increase in the area of synapsin l-puncta. In contrast, E2-BSA was effective to increase the area of synapsin l-puncta. U0126, a inhibitor of ERK, remarkably reduced the area of synapsin l-puncta. It also suppressed the increase in area of synapsin l-puncta induced by E2 as well as E2-BSA. All these results suggested that E2 can affect developing hypothalamic neurons through a non-genomic pathway including ERK cascade. Our studies provide a framework to begin to examine the in vivo role of JNK and ERK in neural development. Less