Differentiation of neural stem cells (NSCs) involves the activation of aerobic metabolism, which is dependent on mitochondrial function. Here, we show that the differentiation of NSCs involves robust increases in mitochondrial mass, mitochondrial DNA (mtDNA) copy number, and respiration capacity. The increased respiration activity renders mtDNA vulnerable to oxidative damage, and NSCs defective for the mitochondrial 8-oxoguanine DNA glycosylase (OGG1) function accumulate mtDNA damage during the differentiation. The accumulated mtDNA damages in ogg1 2/2 cells inhibit the normal maturation of mitochondria that is manifested by reduced cellular levels of mitochondrial encoded complex proteins (complex I[cI], cIII, and cIV) with normal levels of the nuclear encoded cII present. The specific cI activity and inner membrane organization of respiratory complexes are similar in wt and ogg1 2/2 cells, inferring that mtDNA damage manifests itself as diminished mitochondrial biogenesis rather than the generation of dysfunctional mitochondria. Aerobic metabolism increases during differentiation in wild-type cells and to a lesser extent in ogg1 2/2 cells, whereas anaerobic rates of metabolism are constant and similar in both cell types. Our results demonstrate that mtDNA integrity is essential for effective mitochondrial maturation during NSC differentiation. STEM CELLS

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The mechanisms driving innovations that distinguish large taxons are poorly known and essentially accessible via a candidate gene approach. A spectacular acquisition by tunicate larvaceans is the house, a complex extracellular filtration device. Its components are secreted by the oikoplastic epithelium which covers the animal trunk. Here we describe the development of this epithelium in larvae through the formation of specific cellular territories known to produce distinct sets of house proteins (Oikosins). It involves cell divisions and morphological differentiation but very limited cell migration. A diverse set of homeobox genes, most often duplicated in the genome, are transiently and site-specifically expressed in the trunk epithelium at early larval stages. Using RNA interference, we show that two prop duplicates are involved in the differentiation of a region on and around the dorsal midline, regulating morphology and the production of a specific oikosin. Our observations favor a scenario in which multiple homeobox genes and most likely other developmental transcription factors were recruited for this innovation. Their frequent duplications probably predated, but were not required for the emergence of the house.

The frequent repetitive secretion of filter-feeding houses of the tunicate, Oikopleura dioica represents investment of a substantial proportion of total body carbon. Despite this investment, the filterfeeding strategy of pelagic tunicates has been proposed as an adaptation to oligotrophic environments. Here, we examined the capacity of O. dioica to modify its house renewal rate (HRR) and expression of component proteins, oikosins, as well as ingestion rates of different sized particles in response to varying food regimes. There were no significant changes in HRR (0.26 + 0.07 SD house h 21 ) with age or food concentration throughout the life cycle. Our data suggest that the complex pattern of endoreduplicating cycles in the oikoplastic epithelium probably limits the capacity to reduce the energetic output of house replacement as a response to a limiting food environment. On the other hand, at the molecular level, there was differential regulation of component house proteins when animals were cultured in standard versus limiting food regimes. Animals pre-conditioned in each of these regimes and subsequently challenged with an identical mixture of large and small particles exhibited different retention efficiencies of larger food particles. Taken together, these results raise the possibility that a limited ability to modulate house architecture may underlie the differential particle retention efficiencies observed.