C-Jun N-terminal kinase (JNK) is implicated in regulating the various cellular events during neural development that include differentiation, apoptosis and migration. MUK/DLK/ZPK is a MAP kinase kinase kinase (MAPKKK) enzyme that activates JNK via MAP kinase kinases (MAPKK) such as MKK7. We show here that the expression of MUK/DLK/ZPK protein in the developing mouse embryo is almost totally specific for the neural tissues, including central, peripheral, and autonomic nervous systems. The only obvious exception is the liver, in which the protein is temporally expressed at around E11. The expression becomes obvious in the neurons of the brain and neural crest tissues at embryonic day 10 (E10) after neuron production is initiated. By E14, MUK/DLK/ZPK proteins are found in various neural tissues including the brain, spinal cord, sensory ganglia (such as trigeminal and dorsal root ganglia), and the sympathetic and visceral nerves. The localization of MUK/DLK/ZPK protein in neural cells almost consistently overlapped that of betaIII-tubulin, a neuron specific tubulin isoform, and both proteins were more concentrated in axons than in cell bodies and dendrites. The intensely overlapping localization of betaIII-tubulin and MUK/DLK/ZPK indicated that this protein kinase is tightly associated with the microtubules of neurons.