Dynamic expression of SEK1 suggests multiple roles of the gene during embryogenesis and in adult brain of mice.

ABSTRACT

Stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), a member of the MAP kinase (MAPK) superfamily, plays a key role in a variety of cellular processes. It is well established that SAPK/JNK activation is controlled by SEK1/MKK4, an up-stream MAP kinase kinase. To gain insight into the role of SEK1 during embryonic development and in adult life, we examined the temporal and spatial patterns of sek1 expression in mice by using in situ hybridization and immunohistochemical study. Dynamic changes of sek1 expression were observed during embryogenesis. Strong sek1 expression was detected in most of the central nervous system and in liver and thymus during early stages of development. While the sek1 expression in nervous system increases over time, expression in fetal liver and thymus gradually decreases as embryogenesis proceeds. High level of the sek1 expression in the central nervous system was persisted throughout postnatal development and remained at a stable level in adult brain. These observations provide an anatomical basis for the vital role(s) of SEK1 in development, for example, in hepatogenesis and/or neurogenesis. Although SEK1 was widely expressed in adult brain, more strong expression of the sek1 was observed at layers 2 and 6 in cerebral cortex, in Purkinje cells of cerebellum, and also in hypothalamic nuclei. The strongest expression of the sek1 was found in the CA3 region of hippocampus, the region being highly vulnerable to exitotoxicity-induced apoptosis in kainate-treated animal models. Interestingly, SEK1 was localized not only in cytoplasm but in dendrites and/or in nucleus of neurons depending on the regions of adult mouse brain. Taken together, these results suggest multiple roles of the SEK1 during embryogenesis and in adult brain.