The impact of JNK on neuronal migration

Incorrect placement of nerve cells during brain development leaves us at risk of diseases and conditions ranging from epilepsy and mental retardation to schizophrenia and dyslexia. The developing brain produces cells at an impressive rate, with up to 250,000 new cells generated every minute. These newborn cells migrate long distances in sequential waves to settle in the layers that make up the cerebral cortex. If a nerve cell moves too fast or too slow during this journey, it may not take the correct route or reach its appropriate destination. Much knowledge has been accumulated on molecular cues and transcriptional programs regulating cortical development. More recently, components of the c-Jun N-terminal signaling cascade have been brought to light as important intracellular regulators of nerve cell motility. In this chapter, we focus on this family of protein kinases, their upstream activators and downstream targets in the context of neuronal migration. We first present basic information on these molecules, much of which derives from studies outside the nervous system. We then highlight key findings on JNK signaling in brain where it phosphorylates brain-specific proteins that influence microtubule homeostasis. Finally, we summarize recent findings from transgenic mice on the regulation of neuronal migration by JNK cascade components and by JNK substrates.