14 subunits are highly conserved during evolution, have bacterial homologues and are thus considered as ����core���� units of complex I. They are indispensible for the basic catalytic function of the enzyme complex and comprise all mtDNA encoded subunits and seven nuclear encoded subunits, which contain the redox groups and most components of the proton translocation machinery. The exact function of the remaining accessory subunits is CGS 19755 largely unknown. They likely play a role in organization and stabilization of the holoenzyme. Mutations leading to complex I deficiency affect mtDNA and nuclear encoded structural subunits as well as assembly genes such as NDUFAF2, C20RF7, NDUFAF3, NDUFAF4, NUBPL and FOXRED1. Leigh syndrome becomes clinically apparent during the first two years of life, but respiratory chain deficiency may even manifest antenatally. Characteristic neuropathological features of mitochondrial BRL 44408 maleate disorders are often region-specific; such as hypoplasia of the Corpus callosum in pyruvate dehydrogenase complex deficiency or bilateral lesions of the brainstem, striatum and cerebellum in complex I deficiency. We wondered whether such characteristic lesional patterns could be explained by the tissue specific time course of gene expression for important functional components of the respiratory chain during the embryonic-fetal period. Little is known about the antenatal gene expression of respiratory chain components in humans or animals. On the enzyme level Minai et al. investigated various tissues of aborted human fetuses for the activity of respiratory chain activities of the complexes I-V. They found that already at early stages of fetal development the respiratory chain complexes are enzymatically functional, although the absolute activities were lower than after birth. Several animal studies also indicate an up-regulation of mitochondrial biogenesis and gene expression in the postnatal period. In contrast to these mainly biochemical investigations and global gene expression studies, the time course and regional specificity of respiratory chain gene expression during embryonic development had not been investigated before. We thus set out to investigate by in situ hybridization whether the pattern of gene expression for complex I subunits in mice correlates with the pattern of neuropathology and brain dysfunction seen in human patients with complex I deficiency. Hippocampal neurons proliferate prenatally, followed by dynamic growth and differentiation around the neonatal period and synaptogenesis in the first postnatal week. In the second and third postnatal weeks synaptic connections are reinforced through triggered synaptic activity while the maturation is completed around the first month of life. In the hippocampus we observed expression levels and dynamics that differed between the CA regions and the dentate gyrus.